Transcriptional analysis of the B cell germinal center reaction

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 5 - Trang 2639-2644 - 2003
Ulf Klein1, Yuhai Tu1, Gustavo Stolovitzky1, Jeffrey L. Keller1, Joseph Haddad1, Vladan Miljkovic1, Giorgio Cattoretti1, Andrea Califano1, Riccardo Dalla‐Favera1
1Institute for Cancer Genetics, and Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; IBM T. J. Watson Research Center, Yorktown Heights, New York, NY 10598; Division of Pediatric Otolaryngology, Columbia–Presbyterian Medical Center, Babies and Children's Hospital, New York, NY 10032; and First Genetic Trust, Inc., Lyndhurst, NJ 07071

Tóm tắt

The germinal center (GC) reaction is crucial for T cell-dependent immune responses and is targeted by B cell lymphomagenesis. Here we analyzed the transcriptional changes that occur in B cells during GC transit (naïve B cells → centroblasts → centrocytes → memory B cells) by gene expression profiling. Naïve B cells, characterized by the expression of cell cycle-inhibitory and antiapoptotic genes, become centroblasts by inducing an atypical proliferation program lacking c-Myc expression, switching to a proapoptotic program, and down-regulating cytokine, chemokine, and adhesion receptors. The transition from GC to memory cells is characterized by a return to a phenotype similar to that of naïve cells except for an apoptotic program primed for both death and survival and for changes in the expression of cell surface receptors including IL-2 receptor β. These results provide insights into the dynamics of the GC reaction and represent the basis for the analysis of B cell malignancies.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 100 Số 5

2639-2644

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