BAFF is a survival and maturation factor for mouse B cells

Abstract

Human B cell‐activating factor (BAFF) induces mouse surface IgM+ B cells of the immature type from bone marrow and of the immature types 1 and 2 from spleen, as well as of the mature type from spleen to increased longevity in tissue culture. BAFF does so polyclonally and without inducing proliferation in any of these B cell subpopulations. BAFF induces phenotypic and functional maturation of immature to mature B cells so that all immature cells loose C1qRp (AA4.1, 493) expression and type 1 immature cells up‐regulate IgD, CD21 and CD23. Immature B cells of types 1 and 2, upon pre‐incubation with BAFF, change their reactiveness to Ig‐specific antibodies so that they no longer enter apoptosis but now proliferate. However, BAFF does not seem to overcome negative selection of developing immature B cells in vitro.

The anti‐apoptotic factor Bcl‐2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

“…BAFF is a B cell survival factor for transitional type-2 and other B cells in vitro [17,18,23]. In vivo, absence of BAFF signaling results in a severe deficit of mature B cells in BAFF -/-, BAFF-R-deficient and TACI-Ig-Tg mice [2-4, 24, 25].…”

“…Results from in vitro studies rather suggest that BAFF acts as a survival factor on transitional and mature B cells [17,18]. However, the study of BAFF function on follicular or marginal zone B cells in vivo is hampered by the fact that their precursors depend on BAFF.…”

TLR Stimulation Modifies BLyS Receptor Expression in Follicular and Marginal Zone B Cells

“…Furthermore, BLyS has been implicated in several humoral autoimmune disorders and animal models of autoimmunity (13)(14)(15)(16), confirming its function in specificity-based selection. We and others have shown that mature B cells continuously compete for BLyS to survive (10), and that BLyS levels determine the proportion of cells that successfully complete transitional B cell differentiation (4,(17)(18)(19). Among the three known BLyS receptors, BLyS receptor 3 (BR3) interacts solely with BLyS and plays a dominant role in maintaining normal follicular (FO) and marginal zone (MZ) B cell numbers (8,9,11,20,21).…”

Constitutive NF-κB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas

“…[30][31][32][33] In vivo and in vitro studies have demonstrated that BLyS signaling increases the expression of antiapoptotic molecules such as Bcl-2 and promotes cell survival, cell-cycle progression, and proliferation of B cells. [34][35][36][37] Previous studies also have shown that BLyS can activate NF-B2 through the ubiquitin-mediated proteolysis of p100, 27,28 and the NF-B1 pathway through the proteolysis of IB␣ in vitro. 35,38 These studies suggest that activation of NF-B family members play a major role in critical BLyS signaling pathway in the mature B-cell lineage.…”