B Cell Activating Factor Inhibition Impairs Bacterial Immunity by Reducing T Cell-Independent IgM Secretion

B cell activating factor of the tumor necrosis factor family (BAFF) is an essential survival factor for B cells and has been shown to regulate T cell-independent (TI) IgM production. During Ehrlichia muris infection, TI IgM secretion in the spleen was BAFF dependent, and antibody-mediated BAFF neutralization led to an impairment of IgM-mediated host defense. The failure of TI plasmablasts to secrete IgMwas not a consequence of alterations in their generation, survival, or early differentiation, since all occurred normally in infected mice following BAFF neutralization. Gene expression characteristic of plasma cell differentiation was also unaffected by BAFF neutralization in vivo, and except for CD138, plasmablast cell surface marker expression was unaf-fected. IgMwas produced, since it was detected intracellularly, and impaired secretion was not due to a failure to express the IgM secretory exon. Addition of BAFF to plasmablasts in vitro rescued IgM secretion, suggesting that BAFF signaling can directly regulate secretory processes. Our findings indicate that BAFF signaling canmodulate TI host defense by acting at a late stage in B cell differentiation, via its regulation of terminal plasmablast differentiation and/or IgM secretion. In contrast to infections with many other obligately intracellularpathogens, Ehrlichia muris infection generates a T cell-indepen-dent (TI) plasmablast response that is required for IgM-mediated immunity during both acute and chronic infection (1–3). Al-though originally characterized as CD11c-expressing B cells, the TI spleen plasmablasts we have described express a number o