B1b lymphocyte-derived antibodies control Borrelia hermsii independent of Fcα/μ receptor and in the absence of host cell contact

Abstract

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either convalescent or passively immunized mice. Furthermore, adoptively transferred convalescent B1b cells in Rag1(-/-) mice produced specific IgM that also cleared B. hermsii in diffusion chambers independent of complement. These results demonstrate that IgM-mediated clearance of B. hermsii does not require opsonophagocytosis and indicate that a mechanism for in vivo B1b cell-mediated protection is through the generation of bactericidal IgM.

Secreted IgM: New tricks for an old molecule

“…The presence of the Fcα/µR appeared to be largely dispensable for mediating the immune protective role of sIgM following B. hermsii infection, and therefore opsonization of antigen for macrophage uptake . Instead, the receptor has been shown to mediate the endocytosis of IgM‐coated bacteria by B cells and the binding and internalization of sIgM‐antigen complexes by FDC.…”

“…[122][123][124][125] The presence of the Fc /μR appeared to be largely dispensable for mediating the immune protective role of sIgM following B. hermsii infection, and therefore opsonization of antigen for macrophage uptake. 126 Instead, the receptor has been shown to mediate the endocytosis of IgM-coated bacteria by B cells 123,124 and the binding and internalization of sIgM-antigen complexes by FDC. Thus, the receptor can promote antigen processing and presentation to CD4 helper T cells via binding to sIgM and IgA-antigen complexes, 124 while reducing the availability of antigen tethering on the surface of FDC, and thus antigen presentation to B cells.…”

Characterization of a DNA Adenine Methyltransferase Gene of Borrelia hermsii and Its Dispensability for Murine Infection and Persistence

“…SCID mice lack antibody production, including the borreliacidal immunoglobulin M (IgM) antibodies that are rapidly produced after host infection and known to be critical for control of B . hermsii infection [ 38 – 41 ].…”

Generation of Mammalian Host-Adapted Borrelia burgdorferi by Cultivation in Peritoneal Dialysis Membrane Chamber Implantation in Rats

“…Lastly, the DMC model provides a facile means of refining the virulence-related phenotypes of B. burgdorferi mutants that are unable to establish infection within mice (17–20). This procedure also has been used to cultivate B. hermsii (21), pathogenic Leptospira interrogans (22, 23) and avirulent (Lcr-) Yersinia pestis .…”