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BAFF mediates survival of peripheral immature B lymphocytes.
Journal of Experimental Medicine
Date de publication
B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.
Animals, Autoimmunity, B-Cell Activating Factor, B-Lymphocyte Subsets/cytology, B-Lymphocyte Subsets/immunology, Cell Differentiation, Cell Survival, Cells, Cultured, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/immunology, Membrane Proteins/metabolism, Mice, Models, Immunological, Spleen/cytology, Spleen/immunology, Tumor Necrosis Factor-alpha/metabolism
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