Fate Decisions Regulating Bone Marrow and Peripheral B Lymphocyte Development

Adams, 2006, The hematopoietic stem cell in its place, Nat. Immunol., 7, 333, 10.1038/ni1331 Adolfsson, 2001, Upregulation of Flt3 expression within the bone marrow Lin(−)Sca(+)c‐kit(+) stem cell compartment is accompanied by loss of self‐renewal capacity, Immunity, 15, 659, 10.1016/S1074-7613(01)00220-5 Adolfsson, 2005, Identification of Flt3+ lympho‐myeloid stem cells lacking erythro‐megakaryocytic potential: A revised road map for adult blood lineage commitment, Cell, 121, 295, 10.1016/j.cell.2005.02.013 Akashi, 2000, A clongenic common myeloid progenitor that gives rise to all myeloid lineages, Nature, 404, 193, 10.1038/35004599 Allam, 2004, The adaptor protein Bam32 regulates Rac1 activation and actin remodeling through a phosphorylation‐dependent mechanism, J. Biol. Chem., 279, 39775, 10.1074/jbc.M403367200 Allman, 2001, Resolution of three Nonproliferative Immature Splenic B cell subsets reveals multiple selection points during peripheral B cell maturation, J. Immunol., 167, 6834, 10.4049/jimmunol.167.12.6834 Allman, 2003, Thymopoiesis independent of common lymphoid progenitors, Nat. Immunol., 4, 168, 10.1038/ni878 Allman, 1992, Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat‐stable antigenhi and exhibit unique signaling characteristics, J. Immunol., 149, 2533 Allman, 1993, Peripheral B cell maturation. II. Heat‐stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long‐lived marrow‐derived B cells, J. Immunol., 151, 4431 Alt, 1987, Development of the primary antibody repertoire, Science, 238, 1079, 10.1126/science.3317825 Amanna, 2003, Enforced bcl‐xL gene expression restored splenic B lymphocyte development in BAFF‐R mutant mice, J. Immunol., 170, 4593, 10.4049/jimmunol.170.9.4593 Artavanis‐Tsakonas, 1999, Notch signaling: Cell fate control and signal integration in development, Science, 284, 770, 10.1126/science.284.5415.770 Bain, 1994, E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements, Cell, 79, 885, 10.1016/0092-8674(94)90077-9 Barton, 1998, The Ets‐1 transcription factor is required for the development of natural killer cells in mice, Immunity, 9, 555, 10.1016/S1074-7613(00)80638-X Benschop, 2001, Unique signaling properties of B cell antigen receptor in mature and immature B cells: Implications for tolerance and activation, J. Immunol., 167, 4172, 10.4049/jimmunol.167.8.4172 Bjorck, 1998, CD19 + pro‐B cells can give rise to dendritic cells in vitro, J. Immunol., 161, 5795 Borge, 1999, Lymphoid‐restricted development from multipotent candidate murine stem cells: Distinct and complimentary functions of the c‐kit and flt3‐ligands, Blood, 94, 3781, 10.1182/blood.V94.11.3781 Brass, 1999, Assembly requirements of PU.1‐Pip (IRF‐4) activator complexes: Inhibiting function in vivo using fused dimers, EMBO J., 18, 977, 10.1093/emboj/18.4.977 Brendolan, 2007, Development and function of the mammalian spleen, Bioessays, 29, 166, 10.1002/bies.20528 Brines, 1993, Polyclonal activation of immature B cells by preactivated T cells: The role of IL‐4 and CD40 ligand, Int. Immunol., 5, 1445, 10.1093/intimm/5.11.1445 Burrows, 2002, The transient expression of pre‐B cell receptors governs B cell development, Semin. Immunol., 14, 343, 10.1016/S1044-5323(02)00067-2 Busslinger, 2004, Transcriptional control of early B cell development, Annu. Rev. Immunol., 22, 55, 10.1146/annurev.immunol.22.012703.104807 Busslinger, 2000, Lineage commitment in lymphopoiesis, Curr. Opin. Immunol., 12, 151, 10.1016/S0952-7915(99)00065-5 Campos‐Ortega, 1996, Numb diverts notch pathway off the tramtrack, Neuron, 17, 1, 10.1016/S0896-6273(00)80274-3 Cariappa, 2001, The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21, Immunity, 14, 603, 10.1016/S1074-7613(01)00135-2 Carsetti, 1995, Transitional B cells are the target of negative selection in the B cell compartment, J. Exp. Med., 181, 2129, 10.1084/jem.181.6.2129 Carsetti, 2004, Peripheral development of B cells in mouse and man, Immunol. Rev., 197, 179, 10.1111/j.0105-2896.2004.0109.x Casellas, 2001, Contribution of receptor editing to the antibody repertoire, Science, 291, 1541, 10.1126/science.1056600 Casey, 1995, Protein lipidation in cell signaling, Science, 268, 221, 10.1126/science.7716512 Cheng, 1999, A role for lipid rafts in B cell antigen receptor signaling and antigen targeting, J. Exp. Med., 190, 1549, 10.1084/jem.190.11.1549 Chiang, 1999, BSAP/Pax5A expression blocks survival and expansion of early myeloid cells implicating its involvement in maintaining commitment to the B‐lymphocyte lineage, Blood, 94, 3621, 10.1182/blood.V94.11.3621 Chiang, 2001, Role for transcription Pax5A factor in maintaining commitment to the B cell lineage by selective inhibition of granulocyte‐macrophage colony‐stimulating factor receptor expression, J. Immunol., 166, 6091, 10.4049/jimmunol.166.10.6091 Chung, 2001, Cutting edge: Differential sequestration of plasma membrane‐associated B cell antigen receptor in mature and immature B cells into glycosphingolipid‐enriched domains, J. Immunol., 166, 736, 10.4049/jimmunol.166.2.736 Chung, 2002, CD23 defines two distinct subsets of immature B cells which differ in their responses to T cell help signals, Int. Immunol., 14, 157, 10.1093/intimm/14.2.157 Chung, 2003, Incomplete activation of CD4 T cells by antigen‐presenting transitional immature B cells: Implications for peripheral B and T cell responsiveness, J. Immunol., 171, 1758, 10.4049/jimmunol.171.4.1758 Cobb, 2005, Ikaros‐family proteins: In search of molecular functions during lymphocyte development, Curr. Top. Microbiol. Immunol., 290, 29, 10.1007/3-540-26363-2_3 Corcoran, 1998, Impaired immunoglobulin gene rearrangement in mice lacking the IL‐7 receptor, Nature, 391, 904, 10.1038/36122 Dal Porto, 2004, Regulation of BCR signal transduction in B‐1 cells requires the expression of the Src family kinase Lck, Immunity, 21, 443, 10.1016/j.immuni.2004.07.018 Dejardin, 2006, The alternative NF‐kappaB pathway from biochemistry to biology: Pitfalls and promises for future drug development, Biochem. Pharmacol., 72, 1161, 10.1016/j.bcp.2006.08.007 Dekoter, 2000, Regulation of B lymphocyte and macrophage development by graded expression of PU. 1, Science, 288, 1439, 10.1126/science.288.5470.1439 Dekoter, 2002, PU.1 regulates expression of the interleukin‐7 receptor in lymphoid progenitors, Immunity, 16, 297, 10.1016/S1074-7613(02)00269-8 Delogu, 2006, Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells, Immunity, 24, 269, 10.1016/j.immuni.2006.01.012 Dinkel, 1998, The transcription factor early growth response 1 (Egr‐1) advances differentiation of pre‐B and immature B cells, J. Exp. Med., 188, 2215, 10.1084/jem.188.12.2215 Doody, 2001, Signal transduction through Vav‐2 participates in humoral immune responses and B cell maturation, Nat. Immunol., 2, 542, 10.1038/88748 Dorshkind, 1990, Regulation of hemopoiesis by bone marrow stromal cells and their products, Annu. Rev. Immunol., 8, 111, 10.1146/annurev.iy.08.040190.000551 Egawa, 2001, The earliest stages of B cell development require a chemokine stromal cell‐derived factor/pre‐B cell growth‐stimulating factor, Immunity, 15, 323, 10.1016/S1074-7613(01)00185-6 Eisenbeis, 1995, Pip, a novel IRF family member, is a lymphoid‐specific, PU.1‐dependent transcriptional activator, Genes Dev., 9, 1377, 10.1101/gad.9.11.1377 Enver, 1998, Do stem cells play dice?, Blood, 92, 348, 10.1182/blood.V92.2.348 Enzler, 2006, Alternative and classical NF‐kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus‐like disease, Immunity, 25, 403, 10.1016/j.immuni.2006.07.010 Escalante, 2002, Crystal structure of PU.1/IRF‐4/DNA ternary complex, Mol. Cell, 10, 1097, 10.1016/S1097-2765(02)00703-7 Fang, 1998, Self‐reactive B lymphocytes overexpressing Bcl‐xL escape negative selection and are tolerized by clonal anergy and receptor editing, Immunity, 9, 35, 10.1016/S1074-7613(00)80586-5 Fischer, 1994, Lymphoma models for B cell activation and tolerance. X. Anti‐mu‐mediated growth arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization of myc, J. Exp. Med., 179, 221, 10.1084/jem.179.1.221 Fleming, 2001, Pre‐B cell receptor signaling mediates selective response to IL‐7 at the pro‐B to pre‐B cell transition via an ERK/MAP kinase‐dependent pathway, Immunity, 15, 521, 10.1016/S1074-7613(01)00216-3 Flemming, 2003, The adaptor protein SLP‐65 acts as a tumor suppressor that limits pre‐B cell expansion, Nat. Immunol., 4, 38, 10.1038/ni862 Frasca, 2003, Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice, J. Immunol., 170, 719, 10.4049/jimmunol.170.2.719 Fruman, 1999, Impaired B cell development and proliferation in absence of phosphoinositide 3‐kinase p85alpha, Science, 283, 393, 10.1126/science.283.5400.393 Fu, 1998, BLNK: A central linker protein in B cell activation, Immunity, 9, 93, 10.1016/S1074-7613(00)80591-9 Fuentes‐Panana, 2005, Ig alpha/Ig beta complexes generate signals for B cell development independent of selective plasma membrane compartmentalization, J. Immunol., 174, 1245, 10.4049/jimmunol.174.3.1245 Fuentes‐Panana, 2006, Analysis of the individual contributions of Igalpha (CD79a)‐ and Igbeta (CD79b)‐mediated tonic signaling for bone marrow B cell development and peripheral B cell maturation, J. Immunol., 177, 7913, 10.4049/jimmunol.177.11.7913 Futterer, 1998, Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide, J. Mol. Biol., 281, 523, 10.1006/jmbi.1998.1964 Gauld, 2004, Src‐family kinases in B‐cell development and signaling, Oncogene, 23, 8001, 10.1038/sj.onc.1208075 Gauld, 2002, B cell antigen receptor signaling: Roles in cell development and disease, Science, 296, 1641, 10.1126/science.1071546 Geier, 2006, Pre‐BCR signals and the control of Ig gene rearrangements, Semin. Immunol., 18, 31, 10.1016/j.smim.2005.11.001 Georgopoulos, 2002, Haematopoietic cell‐fate decisons, chromatin regulation and ikaros, Nat. Rev. Immunol., 2, 162, 10.1038/nri747 Gerondakis, 2003, The role of Rel/NF‐kappaB transcription factors in B lymphocyte survival, Semin. Immunol., 15, 159, 10.1016/S1044-5323(03)00036-8 Ghia, 1996, Ordering of human bone marrow B lymphocyte precursors by single‐cell polymerase chain reaction analyses of the rearrangement status of the immunoglobulin H and L chain gene loci, J. Exp. Med., 184, 2217, 10.1084/jem.184.6.2217 Gong, 1996, Regulation of an early developmental checkpoint in the B cell pathway by Ig beta, Science, 272, 411, 10.1126/science.272.5260.411 Gorelik, 2004, Cutting edge: BAFF regulates CD21/35 and CD23 expression independent of its B cell survival function, J. Immunol., 172, 762, 10.4049/jimmunol.172.2.762 Grawunder, 1995, Down‐regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement, Immunity, 3, 601, 10.1016/1074-7613(95)90131-0 Gross, 2000, TACI and BCMA are receptors for a TNF homologue implicated in B‐cell autoimmune disease, Nature, 404, 995, 10.1038/35010115 Gross, 2001, TACI‐Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS, Immunity, 15, 289, 10.1016/S1074-7613(01)00183-2 Grossmann, 2000, The anti‐apoptotic activities of Rel and RelA required during B‐cell maturation involve the regulation of Bcl‐2 expression, EMBO J., 19, 6351, 10.1093/emboj/19.23.6351 Hagman, 2006, Transcription factors drive B cell development, Curr. Opin. Immunol., 18, 127, 10.1016/j.coi.2006.01.007 Hardy, 2006, B‐1 B cell development, J. Immunol., 177, 2749, 10.4049/jimmunol.177.5.2749 Hardy, 2006, B‐1 B cells: Development, selection, natural autoantibody and leukemia, Curr. Opin. Immunol., 18, 547, 10.1016/j.coi.2006.07.010 Hardy, 1995, B‐lineage differentiation stages resolved by multiparameter flow cytometry, Ann. N. Y. Acad. Sci., 764, 19, 10.1111/j.1749-6632.1995.tb55800.x Hardy, 2001, B cell development pathways, Annu. Rev. Immunol., 19, 595, 10.1146/annurev.immunol.19.1.595 Hardy, 1991, Resolution and characterization of pro‐B and pre‐pro‐B cell stages in normal mouse bone marrow, J. Exp. Med., 173, 1213, 10.1084/jem.173.5.1213 Harless, 2001, Competition for BLyS‐mediated signaling through Bcmd/BR3 regulates peripheral B lymphocyte numbers, Curr. Biol., 11, 1986, 10.1016/S0960-9822(01)00598-X Hayashi, 2003, Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre‐B cell transition, and tumor suppression in B cell progenitors, Immunity, 18, 825, 10.1016/S1074-7613(03)00142-0 Hofliner, 2004, Analysis of Notch1 function by in vitro T cell differentiation of Pax5 mutant lymphoid progenitors, J. Immunol., 173, 3935, 10.4049/jimmunol.173.6.3935 Holl, 2006, Outside influence: TLRs direct hematopoietic cell fates, Immunity, 24, 667, 10.1016/j.immuni.2006.06.007 Hozumi, 2004, Delta‐like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo, Nat. Immunol., 5, 638, 10.1038/ni1075 Hsu, 2002, Cutting edge: BLyS enables survival of transitional and mature B cells through distinct mediators, J. Immunol., 168, 5993, 10.4049/jimmunol.168.12.5993 Hu, 2001, PU.1/Spi‐B regulation of c‐rel is essential for mature B cell survival, Immunity, 15, 545, 10.1016/S1074-7613(01)00219-9 Igarashi, 2002, Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow, Immunity, 17, 117, 10.1016/S1074-7613(02)00366-7 Iritani, 1997, Control of B cell development by Ras‐mediated activation of Raf, EMBO J., 16, 7019, 10.1093/emboj/16.23.7019 Irvine, 1999, Fringe, notch, and making developmental boundaries, Curr. Opin. Genet. Dev., 9, 434, 10.1016/S0959-437X(99)80066-5 Ishiai, 1999, BLNK required for coupling Syk to PLC gamma 2 and Rac1‐JNK in B cells, Immunity, 10, 117, 10.1016/S1074-7613(00)80012-6 Johnson, 1989, Identification of the alternatively spliced exons of murine CD45 (T200) required for the reactivity with B220 and other T200‐restricted antibodies, J. Exp. Med., 169, 1179, 10.1084/jem.169.3.1179 Jumaa, 2001, The absence of SLP65 and Btk blocks B cell development at the preB cell receptor‐positive stage, Eur. J. Immunol., 31, 2164, 10.1002/1521-4141(200107)31:7<2164::AID-IMMU2164>3.0.CO;2-S Jumaa, 1999, Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP‐65, Immunity, 11, 547, 10.1016/S1074-7613(00)80130-2 Karasuyama, 1996, Surrogate light chain in B cell development, Adv. Immunol., 63, 1, 10.1016/S0065-2776(08)60853-6 Karnell, 2005, Membrane cholesterol content accounts for developmental differences in surface B cell receptor compartmentalization and signaling, J. Biol. Chem., 280, 25621, 10.1074/jbc.M503162200 Karunsky, 2003, Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid‐committed progenitors to Flt3+ dendritic cells in vivo, J. Exp. Med., 198, 305, 10.1084/jem.20030323 Kincade, 1989, Cells and molecules that regulate B lymphopoiesis in bone marrow, Annu. Rev. Immunol., 7, 111, 10.1146/annurev.iy.07.040189.000551 King, 2000, Immunobiology of the immature B cell: Plasticity in the B‐cell antigen receptor‐induced response fine tunes negative selection, Immunol. Rev., 176, 86, 10.1034/j.1600-065X.2000.00609.x King, 1999, Antigen receptor‐induced signal transduction imbalances associated with the negative selection of immature B cells, J. Immunol., 162, 2655 Kishihara, 1993, Normal B lymphocyte development but impaired T cell maturation in CD45‐exon6 protein tyrosine phosphatase‐deficient mice, Cell, 74, 143, 10.1016/0092-8674(93)90302-7 Kitamura, 1992, Targeted disruption of mu chain membrane exon causes loss of heavy‐chain allelic exclusion, Nature, 356, 154, 10.1038/356154a0 Kondo, 1997, Identification of clonogenic common lymphoid progenitors in mouse bone marrow, Cell, 91, 661, 10.1016/S0092-8674(00)80453-5 Kondo, 2000, Cell‐fate conversion of lymphoid‐committed progenitors by instructive actions of cytokines, Nature, 407, 383, 10.1038/35030112 Kondo, 2003, Biology of hematopoietic stem cells and progenitors: Implications for clinical application, Annu. Rev. Immunol., 21, 759, 10.1146/annurev.immunol.21.120601.141007 Kouro, 2002, Relationships between early B‐ and NK‐lineage lymphocyte precursors in bone marrow, Blood, 100, 3672, 10.1182/blood-2002-02-0653 Kraus, 2004, Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer, Cell, 117, 787, 10.1016/j.cell.2004.05.014 Krueger, 2007, Identification of a T lineage‐committed progenitor in adult blood, Immunity, 26, 105, 10.1016/j.immuni.2006.12.004 Kuroda, 2003, Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP‐J signaling pathway, Immunity, 18, 301, 10.1016/S1074-7613(03)00029-3 Kurosawa, 1981, Identification of D segments of immunoglobulin heavy‐chain genes and their rearrangement in T lymphocytes, Nature, 290, 565, 10.1038/290565a0 Labrie, 2005, Bone marrow microenvironmental changes in aged mice compromise V(D)J recombinase activity and B cell generation, Semin. Immunol., 17, 347, 10.1016/j.smim.2005.05.012 Lam, 1997, In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death, Cell, 90, 1073, 10.1016/S0092-8674(00)80373-6 Lee, 1995, Role of Rel‐related factors in control of c‐myc gene transcription in receptor‐mediated apoptosis of the murine B cell WEHI 231 line, J. Exp. Med., 181, 1169, 10.1084/jem.181.3.1169 Leitges, 1996, Immunodeficiency in protein kinase cbeta‐deficient mice, Science, 273, 788, 10.1126/science.273.5276.788 Lentz, 1996, Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in the A/WySnJ mouse, J. Immunol., 157, 598 Li, 1996, Identification of the earliest B lineage stage in mouse bone marrow, Immunity, 5, 527, 10.1016/S1074-7613(00)80268-X Lian, 2002, Murine natural killer cell progenitors and their requirements for development, Semin. Immunol., 14, 453, 10.1016/S1044532302000805 Lin, 1995, Failure of B‐cell differentiation in mice lacking the transcription factor EBF, Nature, 376, 263, 10.1038/376263a0 Lindsley, 2007, Generation of peripheral B cells occurs via two spatially and temporally distinct pathways, Blood, 109, 2521, 10.1182/blood-2006-04-018085 Linton, 2004, Age‐related changes in lymphocyte development and function, Nat. Immunol., 5, 133, 10.1038/ni1033 Liu, 2003, Bcl11a is essential for normal lymphoid development, Nat. Immunol., 4, 525, 10.1038/ni925 Loder, 1999, B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor‐derived signals, J. Exp. Med., 190, 75, 10.1084/jem.190.1.75 Lopes‐Carvalho, 2004, Development and selection of marginal zone B cells, Immunol. Rev., 197, 192, 10.1111/j.0105-2896.2004.0112.x Lu, 2003, IRF‐4,8 orchestrate the pre‐B‐to‐B transition in lymphocyte development, Genes Dev., 17, 1703, 10.1101/gad.1104803 Macdonald, 2001, Notch1 and T‐cell development: Insights from conditional knockout mice, Trends Immunol., 22, 155, 10.1016/S1471-4906(00)01828-7 Mackarehtschian, 1995, Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors, Immunity, 3, 147, 10.1016/1074-7613(95)90167-1 Maier, 2004, Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb‐1 transcription, Nat. Immunol., 5, 1069, 10.1038/ni1119 Maillard, 2004, Mastermind critically regulates Notch‐mediated lymphoid cell fate decisions, Blood, 104, 1696, 10.1182/blood-2004-02-0514 Marshall, 1998, Modulation of the IL‐7 dose‐response threshold during pro‐B cell differentiation is dependent on pre‐B cell receptor expression, J. Immunol., 161, 6038 Marshall‐Clarke, 2000, Immature B lymphocytes from adult bone marrow exhibit a selective defect in induced hyperexpression of major histocompatibility complex class II and fail to show B7. 2 induction, Immunology, 100, 141, 10.1046/j.1365-2567.2000.00035.x Martensson, 2002, The pre‐B cell receptor and its role in proliferation and Ig heavy chain allelic exclusion, Semin. Immunol., 14, 335, 10.1016/S1044-5323(02)00066-0 Martin, 2003, Efficient thymic immigration of B220 + lymphoid‐restricted bone marrow cells with T precursor potential, Nat. Immunol., 4, 866, 10.1038/ni965 Mcmahon, 1995, Activation of the p21ras pathway couples antigen receptor stimulation to induction of the primary response gene egr‐1 in B lymphocytes, J. Exp. Med., 181, 417, 10.1084/jem.181.1.417 Medina, 2005, Genetic networks that regulate B lymphopoiesis, Curr. Opin. Hematol., 12, 203, 10.1097/01.moh.0000160735.67596.a0 Medina, 2001, Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen, Nat. Immunol., 2, 718, 10.1038/90659 Medina, 2004, Assembling a gene regulatory network for specification of the B cell fate, Dev. Cell, 7, 607, 10.1016/j.devcel.2004.08.006 Meffre, 2002, Deletion of immunoglobulin beta in developing B cells leads to cell death, Proc. Natl. Acad. Sci. USA, 99, 11334, 10.1073/pnas.172369999 Meffre, 2000, Antibody regulation of B cell development, Nat. Immunol., 1, 379, 10.1038/80816 Melchers, 2005, The pre‐B‐cell receptor: Selector of fitting immunoglobulin heavy chains for the B‐cell repertoire, Nat. Rev. Immunol., 5, 578, 10.1038/nri1649 Melchers, 1993, The surrogate light chain in B‐cell development, Immunol. Today, 14, 60, 10.1016/0167-5699(93)90060-X Merrell, 2006, Identification of anergic B cells within a wild‐type repertoire, Immunity, 25, 953, 10.1016/j.immuni.2006.10.017 Metcalf, 1998, Lineage commitment and maturation in hematopoietic cells: The case for extrinsic regulation, Blood, 92, 345, 10.1182/blood.V92.2.345b Middendorp, 2005, Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity, Blood, 105, 259, 10.1182/blood-2004-07-2708 Mikkola, 2002, Reversion of B cell commitment upon loss of Pax5 expression, Science, 297, 110, 10.1126/science.1067518 Miller, 2003, The decline in B lymphopoiesis in aged mice reflects loss of very early B‐lineage precursors, J. Immunol., 171, 2326, 10.4049/jimmunol.171.5.2326 Miller, 2005, B cell development and receptor diversity during aging, Curr. Opin. Immunol., 17, 463, 10.1016/j.coi.2005.07.002 Miller, 2006, Space, selection, and surveillance: Setting boundaries with BLys, J. Immunol., 176, 6405, 10.4049/jimmunol.176.11.6405 Min, 2006, Effects of aging on the common lymphoid progenitor to pro‐B cell transition, J. Immunol., 176, 1007, 10.4049/jimmunol.176.2.1007 Monroe, 2005, Molecular mechanisms regulating B cell responsiveness and tolerance, Transplantation, 79, S12, 10.1097/01.TP.0000153291.56965.AD Monroe, 2006, ITAM‐mediated tonic signalling through pre‐BCR and BCR complexes, Nat. Rev. Immunol., 6, 283, 10.1038/nri1808 Montecino‐Rodriguez, 2006, New perspectives in B‐1 B cell development and function, Trends. Immunol., 27, 428, 10.1016/j.it.2006.07.005 Montecino‐Rodriguez, 2007, Fetal B lymphopoiesis and the emergence of B‐1 cell potential, Nat. Rev. Immunol., 7, 213, 10.1038/nri2019 Montecino‐Rodriguez, 2001, Bipotential B‐macrophage progenitors are present in adult bone marrow, Nat. Immunol., 2, 83, 10.1038/83210 Morris, 1992, Antigen presentation for T cell interleukin‐2 secretion is a late acquisition of neonatal B cells, Eur. J. Immunol., 22, 2923, 10.1002/eji.1830221125 Morrison, 1994, The long‐term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype, Immunity, 1, 661, 10.1016/1074-7613(94)90037-X Muljo, 2003, A small molecule Abl kinase inhibitor induces differentiation of Abelson virus‐transformed pre‐B cell lines, Nat. Immunol., 4, 31, 10.1038/ni870 Murre, 1989, A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins, Cell, 56, 777, 10.1016/0092-8674(89)90682-X Nagai, 2006, Toll‐like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment, Immunity, 24, 801, 10.1016/j.immuni.2006.04.008 Nagaoka, 2000, Ras mediates effector pathways responsible for pre‐B cell survival, which is essential for the developmental progression to the late pre‐B cell stage, J. Exp. Med., 192, 171, 10.1084/jem.192.2.171 Nagasawa, 2006, Microenvironmental niches in the bone marrow required for B‐cell development, Nat. Rev. Immunol., 6, 107, 10.1038/nri1780 Nagasawa, 1996, Defects of B‐cell lymphopoiesis and bone‐marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF‐1, Nature, 382, 635, 10.1038/382635a0 Nagata, 1997, The Ig alpha/Igbeta heterodimer on mu‐negative proB cells is competent for transducing signals to induce early B cell differentiation, Immunity, 7, 559, 10.1016/S1074-7613(00)80377-5 Nemazee, 2006, Receptor editing in lymphocyte development and central tolerance, Nat. Rev. Immunol., 6, 728, 10.1038/nri1939 Nichogiannopoulou, 1999, Defects in hemopoietic stem cell activity in Ikaros mutant mice, J. Exp. Med., 190, 1201, 10.1084/jem.190.9.1201 Niiro, 2002, Regulation of B‐cell fate by antigen‐receptor signals, Nat. Rev. Immunol., 2, 945, 10.1038/nri955 Niiro, 2002, The B lymphocyte adaptor molecule of 32 kD (Bam32) regulates B cell antigen receptor signaling and cell survival, J. Exp. Med., 195, 143, 10.1084/jem.20011524 Norvell, 1996, Acquisition of surface IgD fails to protect from tolerance‐induction. Both surface IgM‐ and surface IgD‐mediated signals induce apoptosis of immature murine B lymphocytes, J. Immunol., 156, 1328 Norvell, 1995, Engagement of the antigen‐receptor on immature murine B lymphocytes results in death by apoptosis, J. Immunol., 154, 4404 Nutt, 1999, Commitment to the B‐lymphoid lineage depends on the transcription factor Pax5, Nature, 401, 556, 10.1038/44076 Ohnishi, 2003, The nonimmunoglobulin portion of lambda5 mediates cell‐autonomous pre‐B cell receptor signaling, Nat. Immunol., 4, 849, 10.1038/ni959 Osmond, 1993, The turnover of B‐cell populations, Immunol. Today, 14, 34, 10.1016/0167-5699(93)90322-C Osmond, 1998, Murine B lymphopoiesis: Towards a unified model, Immunol. Today, 19, 65, 10.1016/S0167-5699(97)01203-6 Otero, 2003, CD19 function in early and late B cell development. II. CD19 facilitates the pro‐B/pre‐B transition, J. Immunol., 171, 5921, 10.4049/jimmunol.171.11.5921 Pani, 1997, The motheaten mutation rescues B cell signaling and development in CD45‐deficient mice, J. Exp. Med., 186, 581, 10.1084/jem.186.4.581 Papavasiliou, 1995, The cytoplasmic domains of immunoglobulin (Ig) alpha and Ig beta can independently induce the precursor B cell transition and allelic exclusion, J. Exp. Med., 182, 1389, 10.1084/jem.182.5.1389 Pappu, 1999, Requirement for B cell linker protein (BLNK) in B cell development, Science, 286, 1949, 10.1126/science.286.5446.1949 Patke, 2006, BAFF controls B cell metabolic fitness through a PKC beta‐ and Akt‐dependent mechanism, J. Exp. Med., 203, 2551, 10.1084/jem.20060990 Payne, 1999, Loss of c‐kit accompanies B lineage commitment and acquisition of CD45R in most murine B lymphocyte precursors, Blood, 94, 713, 10.1182/blood.V94.2.713 Pelanda, 2006, Receptor editing for better or for worse, Curr. Opin. Immunol., 18, 184, 10.1016/j.coi.2006.01.005 Pelayo, 2005, Lymphoid progenitors and primary routes to becoming cells of the immune system, Curr. Opin. Immunol., 17, 100, 10.1016/j.coi.2005.01.012 Pelayo, 2006, Life before the pre‐B cell receptor checkpoint: Specification and commitment of primitive lymphoid progenitors in adult bone marrow, Semin. Immunol., 18, 2, 10.1016/j.smim.2005.10.005 Perry, 2003, Characterization of thymic progenitors in adult use bone marrow, J. Immunol., 170, 1877, 10.4049/jimmunol.170.4.1877 Perry, 2004, L‐selectin defines a bone marrow analog to the thymic early T‐lineage progenitor, Blood, 103, 2990, 10.1182/blood-2003-09-3030 Peschon, 1994, Early lymphocyte expansion is severely impaired in interleukin 7 receptor‐deficient mice, J. Exp. Med., 180, 1955, 10.1084/jem.180.5.1955 Petrie, 2007, Early commitment: T cell progenitors in the blood, Immunity, 26, 7, 10.1016/j.immuni.2007.01.003 Petro, 2002, Transitional type 1 and 2 B lymphocyte subsets are differentially responsive to antigen receptor signaling, J. Biol. Chem., 277, 48009, 10.1074/jbc.M200305200 Pike, 1996, Localization and turnover of phosphatidylinositol 4,5‐bisphosphate in caveolin‐enriched membrane domains, J. Biol. Chem., 271, 26453, 10.1074/jbc.271.43.26453 Pillai, 2005, Marginal zone B cells, Annu. Rev. Immunol., 23, 161, 10.1146/annurev.immunol.23.021704.115728 Pourquie, 1999, Notch around the clock, Curr. Opin. Genet. Dev., 9, 559, 10.1016/S0959-437X(99)00011-8 Pui, 1999, Notch1 expression in early lymphopoiesis influences B versus T lineage determination, Immunity, 11, 299, 10.1016/S1074-7613(00)80105-3 Radtke, 1999, Deficient T cell fate specification in mice with an induced inactivation of Notch1, Immunity, 10, 547, 10.1016/S1074-7613(00)80054-0 Rawlings, 1994, Bruton's tyrosine kinase is a key regulator in B‐cell development, Immunol. Rev., 138, 105, 10.1111/j.1600-065X.1994.tb00849.x Refaeli, 2005, The protooncogene MYC can break B cell tolerance, Proc. Natl. Acad. Sci. USA, 102, 4097, 10.1073/pnas.0409832102 Reth, 1987, Activation of V kappa gene rearrangement in pre‐B cells follows the expression of membrane‐bound immunoglobulin heavy chains, EMBO J., 6, 3299, 10.1002/j.1460-2075.1987.tb02649.x Rolink, 2000, Precursor B cell receptor‐dependent B cell proliferation and differentiation does not require the bone marrow or fetal liver environment, J. Exp. Med., 191, 23, 10.1084/jem.191.1.23 Rolink, 2002, BAFF is a survival and maturation factor for mouse B cells, Eur. J. Immunol., 32, 2004, 10.1002/1521-4141(200207)32:7<2004::AID-IMMU2004>3.0.CO;2-5 Rolli, 2002, Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop, Mol. Cell, 10, 1057, 10.1016/S1097-2765(02)00739-6 Rossi, 2005, Cell intrinsic alterations underlie hematopoietic stem cell aging, Proc. Natl. Acad. Sci. USA, 102, 9194, 10.1073/pnas.0503280102 Rumfelt, 2006, Lineage specification and plasticity in CD19− early B cell precursors, J. Exp. Med., 203, 675, 10.1084/jem.20052444 Saijo, 2002, Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha, J. Exp. Med., 195, 1647, 10.1084/jem.20020408 Saijo, 2003, Essential role of Src‐family protein tyrosine kinases in NF‐kappaB activation during B cell development, Nat. Immunol., 4, 274, 10.1038/ni893 Saito, 2003, Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development, Immunity, 18, 675, 10.1016/S1074-7613(03)00111-0 Samardzic, 2002, Reduction of marginal zone B cells in CD22‐deficient mice, Eur. J. Immunol., 32, 561, 10.1002/1521-4141(200202)32:2<561::AID-IMMU561>3.0.CO;2-H Sandel, 1999, Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter, Immunity, 10, 289, 10.1016/S1074-7613(00)80029-1 Sandel, 2001, Definition of a novel cellular constituent of the bone marrow that regulates the response of immature B cells to B cell antigen receptor engagement, J. Immunol., 166, 5935, 10.4049/jimmunol.166.10.5935 Sasaki, 2004, TNF family member B cell‐activating factor (BAFF) receptor‐dependent and ‐independent roles for BAFF in B cell physiology, J. Immunol., 173, 2245, 10.4049/jimmunol.173.4.2245 Sasaki, 2006, Canonical NF‐kappaB activity, dispensable for B cell development, replaces BAFF‐receptor signals and promotes B cell proliferation upon activation, Immunity, 24, 729, 10.1016/j.immuni.2006.04.005 Sater, 1998, B cell receptor‐induced apoptosis in primary transitional murine B cells: Signaling requirements and modulation by T cell help, Int. Immunol., 10, 1673, 10.1093/intimm/10.11.1673 Schebesta, 2002, Control of pre‐BCR signaling by Pax5‐dependent activation of the BLNK gene, Immunity, 17, 473, 10.1016/S1074-7613(02)00418-1 Schiemann, 2001, An essential role for BAFF in the normal development of B cells through a BCMA‐independent pathway, Science, 293, 2111, 10.1126/science.1061964 Schwartz, 2003, T cell anergy, Annu. Rev. Immunol., 21, 305, 10.1146/annurev.immunol.21.120601.141110 Schwarz, 2004, Circulating hematopoietic progenitors with T lineage potential, Nat. Immunol., 5, 953, 10.1038/ni1101 Schweighoffer, 2003, Unexpected requirement for ZAP‐70 in pre‐B cell development and allelic exclusion, Immunity, 18, 523, 10.1016/S1074-7613(03)00082-7 Scott, 1987, Lymphoma models for B cell activation and tolerance. VI. Reversal of anti‐Ig‐mediated negative signaling by T cell‐derived lymphokines, J. Immunol., 139, 3924 Scott, 1997, PU.1 functions in a cell‐autonomous manner to control the differentiation of multipotential lymphoid‐myeloid progenitors, Immunity, 6, 437, 10.1016/S1074-7613(00)80287-3 Seet, 2004, Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A, J. Exp. Med., 199, 1689, 10.1084/jem.20032202 Shahaf, 2004, Screening of alternative models for transitional B cell maturation, Int. Immunol., 16, 1081, 10.1093/intimm/dxh109 Shaw, 1999, Induction of Ig light chain gene rearrangement in heavy chain‐deficient B cells by activated Ras, Proc. Natl. Acad. Sci. USA, 96, 2239, 10.1073/pnas.96.5.2239 Shaw, 1999, Activated Ras signals developmental progression of recombinase‐activating gene (RAG)‐deficient pro‐B lymphocytes, J. Exp. Med., 189, 123, 10.1084/jem.189.1.123 Shigematsu, 2004, Plasmacytoid dendritic cells activate lymphoid‐specific genetic programs irrespective of thier cellular origin, Immunity, 21, 43, 10.1016/j.immuni.2004.06.011 Shinohara, 2005, PKC beta regulates BCR‐mediated IKK activation by facilitating the interaction between TAK1 and CARMA1, J. Exp. Med., 202, 1423, 10.1084/jem.20051591 Sims, 2005, Identification and characterization of circulating human transitional B cells, Blood, 105, 4390, 10.1182/blood-2004-11-4284 Sitnicka, 2002, Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool, Immunity, 17, 463, 10.1016/S1074-7613(02)00419-3 Sitnicka, 2003, Complementary signaling through flt3 and interleukin‐7 receptor alpha is indispensable for fetal and adult B cell genesis, J. Exp. Med., 198, 1495, 10.1084/jem.20031152 Smith, 2003, Cutting edge: B cell receptor signals regulate BLyS receptor levels in mature B cells and their immediate progenitors, J. Immunol., 170, 5820, 10.4049/jimmunol.170.12.5820 Sommer, 2005, Phosphorylation of the CARMA1 linker controls NF‐kappaB activation, Immunity, 23, 561, 10.1016/j.immuni.2005.09.014 Spangrude, 1988, Purification and characterization of mouse hematopoietic stem cells, Science, 241, 58, 10.1126/science.2898810 Sproul, 2000, Cutting edge: B cell antigen receptor signaling occurs outside lipid rafts in immature B cells, J. Immunol., 165, 6020, 10.4049/jimmunol.165.11.6020 Srivastava, 2005, Characterization of marginal zone B cell precursors, J. Exp. Med., 202, 1225, 10.1084/jem.20051038 Stadanlick, 2006, Unraveling the warp and weft of B cell fate, Immunity, 25, 395, 10.1016/j.immuni.2006.09.001 Stauffer, 1997, Compartmentalized IgE receptor‐mediated signal transduction in living cells, J. Cell. Biol., 139, 1447, 10.1083/jcb.139.6.1447 Stephan, 1998, Impaired ability of bone marrow stromal cells to support B‐lymphopoiesis with age, Blood, 91, 75, 10.1182/blood.V91.1.75 Su, 2002, Transitional B lymphocyte subsets operate as distinct checkpoints in murine splenic B cell development, J. Immunol., 168, 2101, 10.4049/jimmunol.168.5.2101 Su, 2004, Signaling in transitional type 2 B cells is critical for peripheral B‐cell development, Immunol. Rev., 197, 161, 10.1111/j.0105-2896.2004.0102.x Su, 2003, LAT links the pre‐BCR to calcium signaling, Immunity, 19, 295, 10.1016/S1074-7613(03)00202-4 Sun, 1991, An inhibitory domain of E12 transcription fctor prevents DNA binding in E12 homodimers but not in E12 heterodimers, Cell, 64, 459, 10.1016/0092-8674(91)90653-G Suzuki, 1999, Xid‐like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3‐kinase, Science, 283, 390, 10.1126/science.283.5400.390 Tanigaki, 2002, Notch‐RBP‐J signaling is involved in cell fate determination of marginal zone B cells, Nat. Immunol., 3, 443, 10.1038/ni793 Tedford, 2001, Compensation between Vav‐1 and Vav‐2 in B cell development and antigen receptor signaling, Nat. Immunol., 2, 548, 10.1038/88756 Ten Boekel, 1997, Changes in the V(H) gene repertoire of developing precursor B lymphocytes in mouse bone marrow mediated by the pre‐B cell receptor, Immunity, 7, 357, 10.1016/S1074-7613(00)80357-X Thompson, 2001, BAFF‐R, a newly identified TNF receptor that specifically interacts with BAFF, Science, 293, 2108, 10.1126/science.1061965 Tokoyoda, 2004, Cellular niches controlling B lymphocyte behavior within bone marrow during development, Immunity, 20, 707, 10.1016/j.immuni.2004.05.001 Tretter, 2003, Mimicry of pre‐B cell receptor signaling by activation of the tyrosine kinase Blk, J. Exp. Med., 198, 1863, 10.1084/jem.20030729 Tudor, 2000, Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events, Immunity, 12, 335, 10.1016/S1074-7613(00)80186-7 Turner, 1997, Syk tyrosine kinase is required for the positive selection of immature B cells into the recirculating B cell pool, J. Exp. Med., 186, 2013, 10.1084/jem.186.12.2013 Ueda, 2004, Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression, J. Exp. Med., 199, 47, 10.1084/jem.20031104 Ueda, 2005, Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow, J. Exp. Med., 201, 1771, 10.1084/jem.20041419 Underhill, 2007, The many faces of ITAMs, Trends Immunol., 28, 66, 10.1016/j.it.2006.12.004 Von Freeden‐Jeffry, 1995, Lymphopenia in interleukin (IL)‐7 gene‐deleted mice identifies IL‐7 as a nonredundant cytokine, J. Exp. Med., 181, 1519, 10.1084/jem.181.4.1519 Walmsley, 2003, Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling, Science, 302, 459, 10.1126/science.1089709 Wang, 2000, Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors, Immunity, 13, 25, 10.1016/S1074-7613(00)00005-4 Wang, 2007, Association of the pre‐B cell receptor (BCR) expression level with the quality of pre‐BII cell differentiation reveals hierarchical pre‐BCR function, Mol. Immunol., 44, 1776, 10.1016/j.molimm.2006.07.301 Wang, 2001, A VH12 transgenic mouse exhibits defects in pre‐B cell development and is unable to make IgM + B cells, J. Immunol., 167, 1254, 10.4049/jimmunol.167.3.1254 Wardemann, 2003, Predominant autoantibody production by early human B cell precursors, Science, 301, 1374, 10.1126/science.1086907 Weinmaster, 2000, Notch signal tranduction: A real rip and more, Curr. Opin. Genet. Dev., 10, 363, 10.1016/S0959-437X(00)00097-6 Wu, 1999, Fringe: Defining borders by regulating the Notch pathway, Curr. Opin. Neurobiol., 9, 537, 10.1016/S0959-4388(99)00020-3 Wu, 1996, Inhibition of c‐myc expression induces apoptosis of WEHI 231 murine B cells, Mol. Cell Biol., 16, 5015, 10.1128/MCB.16.9.5015 Xie, 2004, Stepwise reprogramming of B cells into macrophages, Cell, 117, 663, 10.1016/S0092-8674(04)00419-2 Xu, 2000, B cell development and activation defects resulting in xid‐like immunodeficiency in BLNK/SLP‐65‐deficient mice, Int. Immunol., 12, 397, 10.1093/intimm/12.3.397 Yamazaki, 2002, Essential immunoregulatory role for BCAP in B cell development and function, J. Exp. Med., 195, 535, 10.1084/jem.20011751 Yan, 2001, Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency, Curr. Biol., 11, 1547, 10.1016/S0960-9822(01)00481-X Yellen, 1991, Signaling through surface IgM in tolerance‐susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice, J. Immunol., 146, 1446 Yokota, 1999, Development of peripheral lymphoid organs and natural killer cells depends on the helix‐loop‐helix inhibitor Id2, Nature, 397, 702, 10.1038/17812 Zhuang, 1994, The helix‐loop‐helix gene E2A is required for B cell formation, Cell, 79, 875, 10.1016/0092-8674(94)90076-0 Zou, 1998, Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development, Nature, 393, 595, 10.1038/31269