Predominant Autoantibody Production by Early Human B Cell Precursors

American Association for the Advancement of Science (AAAS) - Tập 301 Số 5638 - Trang 1374-1377 - 2003
Hedda Wardemann1,2,3,4,5, Sergey Yurasov1,2,3,5, Anne Schaefer1,2,3,4,5, James W. Young1,2,3,4, Eric Meffre1,2,3,5, Michel C. Nussenzweig1,2,3,4,5
1Allogeneic Bone Marrow Transplant and Clinical Immunology Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
2Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
3Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
4Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
5Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA.

Tóm tắt

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.

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We thank K. Velinzon and K. Gordon for help with the single cell sorter and all members of the Nussenzweig laboratory and E. Besmer for help with the manuscript. Supported by grants from NIH and the Leukemia-Lymphoma Society (M.C.N. and J.W.Y.) and from the Dana Foundation (E.M.). M.C.N. is a Howard Hughes Medical Institute investigator.

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American Association for the Advancement of Science (AAAS)

Tập 301 Số 5638

1374-1377

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