Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2003-07, Vol.112 (2), p.286-297, Article 286

Ort / Verlag

American Society for Clinical Investigation

Erscheinungsjahr

2003

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.