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BAFF selectively enhances the survival of plasmablasts generated from human memory B cells


Avery, DT; Kalled, SL; Ellyard, JI; Ambrose, C; Bixler, SA; Thien, M; Brink, R; Mackay, F; Hodgkin, PD; Tangye, SG
2003-07
JOURNAL OF CLINICAL INVESTIGATION
Journal Article
112
2
286-297
The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors - transmembrane activator of and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R). To elucidate the contribution of BAFF to the differentiation of B cells into ISCs, we tracked the fate of human memory B cells stimulated with BAFF or CD40L. BAFF and CD40L significantly increased the overall number of surviving B cells. This was achieved via distinct mechanisms. CD40L induced proliferation of nondifferentiated blasts,. while BAFF prevented apoptosis of ISCs without enhancing proliferation. The altered responsiveness of activated memory B cells to CD40L and BAFF correlated with changes in surface phenotype such that expression of CD40 and BAFF-R were reduced on ISCs while BCMA was induced. These results suggest BAFF may enhance humoral immunity in vivo by promoting survival of ISCs via a BCMA-dependent mechanism. These findings have wide-ranging implications for the treatment of human immunodeficiencies as well as autoimmune diseases.
AMER SOC CLINICAL INVESTIGATION INC
NECROSIS-FACTOR FAMILY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IGA-DEFICIENT PATIENTS; LYMPHOCYTE STIMULATOR; AUTOIMMUNE-DISEASE; MARGINAL ZONE; CD40 LIGAND; MATURATION PROTEIN; IMMUNE-RESPONSES; MEMBER TALL-1
10.1172/JCI200318025
Refer to copyright notice on published article.

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Creation Date 2003-07-01 12:00:00