To determine the role of the pleiotropic cytokine TGF-β in B cells, we generated mice lacking the TGF-β receptor (TβR) type II selectively in this cell type through conditional mutagenesis (Cre/loxP). The absence of TβRII in B cells leads to a reduced life span of conventional B cells, expansion of peritoneal B-1 cells, B cell hyperplasia in Peyer's patches, elevated serum immunoglobulin, and substantial IgG3 responses to a normally weak immunogen. This B cell hyperresponsiveness is associated with a virtually complete serum IgA deficiency. The data reveal differential roles of TβR in homeostasis and antigen responsiveness of B cell subpopulations and establish a critical function of the TGF-β receptor ligand pair in the induction of IgA responses in vivo.