B cell activating factor of the TNF family (BAFF), plays critical roles in B cell survival, activation, differentiation, and antibody (Ab) production. BAFF binds to three receptors: BAFF‐R, transmembrane activator and calcium‐modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen. While BAFF‐R is the primary receptor for B cell costimulation by BAFF, TACI is reported to serve as a positive or negative regulator for B cell responses depending on conditions. To determine the real role of TACI in B cell responses, we examined the functional relationship between TACI and BAFF‐R in Ab production from human peripheral blood B cells using agonistic mAb. BAFF‐R and CD40 enhanced IgG secretion and B cell proliferation, which were inhibited by TACI. Although TACI induced mild B cell apoptosis, its extent did not correlate with that of TACI‐mediated inhibition of IgG secretion. In addition, TACI inhibited B‐lymphocyte‐induced maturation protein‐1 expression, IgG secretion from previously IgG‐negative selected B cells, and activation‐induced cytidine deaminase expression enhanced by BAFF‐R and CD40. Importantly, BAFF‐R and CD40 enhanced B cell responsiveness to TACI‐mediated suppression. Thus, BAFF may attenuate T cell‐independent and ‐dependent B cell responses by TACI.

See accompanying commentary http://dx.doi.org/10.1002/eji.200636914