The B lymphocyte‐activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF‐R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation‐inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll‐like receptor agonists (TLR‐A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up‐regulated TACI expression, while BAFF‐R was only up‐regulated by CpG ODN. CpG ODN pretreatment up‐regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF‐ and APRIL‐mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF‐ or APRIL‐induced Ig secretion because B lymphocytes from TACI‐knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN‐pretreated and BAFF‐ or APRIL‐stimulated B cells. Thus, CpG ODN‐induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.