TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo

Abstract

To determine the role of the pleiotropic cytokine TGF-beta in B cells, we generated mice lacking the TGF-beta receptor (TbetaR) type II selectively in this cell type through conditional mutagenesis (Cre/loxP). The absence of TbetaRII 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 TbetaR in homeostasis and antigen responsiveness of B cell subpopulations and establish a critical function of the TGF-beta receptor ligand pair in the induction of IgA responses in vivo.