An interfering form of Blimp-1 increases IgM secreting plasma cells and blocks maturation of peripheral B cells.

B lymphocyte-induced maturation protein-1 (Blimp-1) can drive plasmacytic differentiation in cultured cell models. To determine the role of Blimp-1 in B cell development in vivo, we have generated transgenic mice expressing an interfering truncated form of Blimp-1 (TBlimp) under the control of an immunoglobulin heavy chain promoter and intronic (E) enhancer. TBlimp-transgenic mice have elevated serum IgM and a prolonged IgM response. This effect is due to an increased number of short-lived, IgM-secreting plasma cells resulting from increased proliferation and prolonged survival. In addition, TBlimp-transgenic mice have a developmental defect in the generation of mature B cells in the spleen. These results show that in vivo Blimp-1 plays a fundamental role in the control of the life span and exit from the cell cycle of IgM secreting plasma cells.