Baff Mediates Survival of Peripheral Immature B Lymphocytes

TLDR

B cell maturation is a highly selective process requiring precise differentiation and survival cues, and the TNF family member BAFF promotes BCR‑mediated proliferation and has been implicated in B cell survival, as shown by reduced peripheral B cells when BAFF is blocked and increased Bcl‑2 in BAFF transgenic mice, while immature transitional B cells undergo negative selection to maintain self‑tolerance. The study aimed to evaluate BAFF’s in vitro effect on the survival of lymphocytes from primary and secondary lymphoid organs. In vitro assays were conducted on lymphocytes isolated from primary and secondary lymphoid tissues to test BAFF’s survival effect. BAFF induced survival of splenic transitional type 2 (T2) B cells, enabling their differentiation into mature B cells upon BCR signaling; T2 and marginal zone B cell compartments were enlarged in BAFF transgenic mice, and excessive BAFF‑mediated survival of peripheral immature B cells may promote autoreactive B cell emergence and maturation skewed toward the marginal zone, providing new insights into B cell maturation and tolerance mechanisms.

Abstract

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.