BAFF selectively enhances the survival of plasmablasts generated from human memory B cells
Danielle T. Avery, … , Philip D. Hodgkin, Stuart G. Tangye
Danielle T. Avery, … , Philip D. Hodgkin, Stuart G. Tangye
Published July 15, 2003
Citation Information: J Clin Invest. 2003;112(2):286-297. https://doi.org/10.1172/JCI18025.
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Article Immunology

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

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.

Authors

Danielle T. Avery, Susan L. Kalled, Julia I. Ellyard, Christine Ambrose, Sarah A. Bixler, Marilyn Thien, Robert Brink, Fabienne Mackay, Philip D. Hodgkin, Stuart G. Tangye

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BAFF promotes the generation of CD38+ B cells from activated memory B ce...
BAFF promotes the generation of CD38+ B cells from activated memory B cells. (a) The scheme of the two-step culture system used. CFSE-labeled memory B cells were initially cultured with CD40L and IL-2/IL-10 for 4 days, harvested, washed, and then recultured with media (b–d) or IL-2/IL-10 (e–g) alone (black bars) or in the presence of CD40L (white bars) or BAFF (gray bars). After an additional 4 days, the total number of cells (b and e) and percentage of CD38+ B cells (c and f) in each culture were determined. The number of CD38– and CD38+ B cells (d and g) was calculated by multiplying total cell number by the frequency of CD38– and CD38+ cells, respectively. The values represent the mean ± SEM of four (b–d) or five (e–g) experiments. The horizontal lines in b and e indicate the mean number of B cells present at the beginning of the secondary culture.*P < 0.05; **P < 0.01; ***P < 0.001.