We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
BAFF selectively enhances the survival of plasmablasts generated from human memory B cells.
- Authors
Avery, Danielle T; Kalled, Susan L; Ellyard, Julia I; Ambrose, Christine; Bixler, Sarah A; Thien, Marilyn; Brink, Robert; Mackay, Fabienne; Hodgkin, Philip D; Tangye, Stuart G
- Abstract
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.
- Publication
The Journal of clinical investigation, 2003, Vol 112, Issue 2, p286
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI18025