Protective CD4 T cell-independent IgM responses impairs the production of isotype-switched antibodies during intracellular bacterial infection (133.14)

Abstract

Abstract Ehrlichia muris, an intracellular tick-borne pathogen, generates a CD4 T cell independent (TI) protective response in C57BL/6 mice. At peak infection, the response is accompanied by the expansion splenic extrafollicular CD11clo-expressing plasmablasts that produce antigen-specific IgM. Using secretory IgM (sIgM)-deficient mice and activation-induced adenosine deaminase (AID)-deficient mice, which are unable to undergo antibody class-switching, we demonstrated that IgG is dispensable for immunity and unmutated IgM was sufficient for protection to challenge infection with a highly virulent ehrlichia. Furthermore, while IgM-secreting cells were abundant in the spleen, prior to day 21, IgG was largely absent and instead produced in infected LNs. Thus, the robust IgM response impaired the formation of germinal centers and production IgG-secreting cells in the spleen. These findings, in turn, suggested that ehrlichial infection might suppress the spleen's ability to produce isotype-switched antibodies to blood borne antigens or pathogens. Indeed, E. muris infected-mice immunized with NP-CGG exhibited an impaired NP-specific IgG response. Thus, our studies demonstrate a major protective role for CD4 T cell-independent IgM during intracellular bacterial infection, and suggest a mechanism whereby a T cell-independent response may suppress T-dependent responses during co-infecting pathogens.