BAFF mediates survival of peripheral immature B lymphocytes

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Batten, M; Groom, J; Cachero, TG; Qian, F; Schneider, P; Tschopp, J; Browning, JL; Mackay, FDate
2000-11-20Source Title
Journal of Experimental MedicinePublisher
ROCKEFELLER UNIV PRESSAffiliation
Medical Biology (W.E.H.I.)Microbiology and Immunology
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Batten, M., Groom, J., Cachero, T. G., Qian, F., Schneider, P., Tschopp, J., Browning, J. L. & Mackay, F. (2000). BAFF mediates survival of peripheral immature B lymphocytes. JOURNAL OF EXPERIMENTAL MEDICINE, 192 (10), pp.1453-1465. https://doi.org/10.1084/jem.192.10.1453.Access Status
Open AccessAbstract
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.
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