BAFF mediates survival of peripheral immature B lymphocytes

B cell maturation is a very selective process that requires finely tuned di fferentiation and survival signals. B cell activation factor from the TNF f amily (BAFF) is a TNF family member that binds to 13 cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in 13 cell su rvival was suggested by the observation of reduced peripheral B cell number s in mice treated with reagents blocking BAFF, and high Bcl-2 levels detect ed in B cells from BAFF transgenic (Tg) mice. We tested in vitro the surviv al effect of BAFF on lymphocytes derived from primary and secondary lymphoi d organs. BAFF induced survival of a subset of splenic immature 13 cells, r eferred 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 sign als through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. immature transitional 13 cells are targets for negative selection, a feature thought to promote self-toler ance. These findings support a model in which excessive BAFF-mediated survi val of peripheral immature B cells contributes to the emergence and maturat ion of autoreactive B cells, skewed towards the MZ compartment. This work p rovides new clues on mechanisms regulating B cell maturation and tolerance.