CpG inhibits pro-B cell expansion through a cathepsin B-dependent mechanism.

TLR9 is expressed in cells of the innate immune system, as well as in B lymphocytes and their progenitors. We investigated the effect of the TLR9 ligand CpG DNA on the proliferation of pro-B cells. CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell death through a pathway that requires the expression of cathepsin B. This pathway is operative in Rag-deficient mice carrying an SP6 transgene, in which B lymphopoiesis is compromised, to reduce the size of the B lymphocyte precursor compartments in the bone marrow. Thus, TLR9 signals can regulate B lymphopoiesis in vivo.