BAFF neutralization blocks T cell-independent IgM production (70.3)

Abstract

Abstract Infection of mice with the intracellular bacterium Ehrlichia muris induces a protective T cell-independent (TI) IgM response. The TI IgM produced during acute infection is secreted almost exclusively by a population of CD11c-expressing B cell plasmablasts in the spleen. We investigated the role of B cell activating factor of the TNF family (BAFF) on the generation of the IgM-secreting plasmablasts. To this end, we neutralized BAFF in vivo using a monoclonal antibody directed against murine BAFF. Blockade of BAFF in infected mice did not affect the generation of splenic plasmablasts; however, treatment nearly eliminated the number of antigen-specific IgM-secreting cells, serum IgM titers were reduced, and the plasmablasts failed to express cell-surface CD138. Analysis of mRNA expression in FACS-sorted plasmablasts from anti-BAFF and isotype control-treated mice revealed no differences in transcript levels of prdm1 and xbp1, genes encoding the transcription factors Blimp-1 and XBP-1, which are essential for plasma cell differentiation. Thus, our data indicate that BAFF signaling regulates a checkpoint in plasmablast differentiation, downstream of Blimp-1 and XBP-1 transcription, but prior to CD138 expression.