Antigen-driven induction of polyreactive IgM during intracellular bacterial infection.
Polyreactivity is well known as a property of natural IgM produced by B-1 cells. We demonstrate that polyreactive IgM is also generated during infection of mice with Ehrlichia muris, a tick-borne intracellular bacterial pathogen. The polyreactive IgM bound self and foreign Ags, including single-stranded and double-stranded DNA, insulin, thyroglobulin, LPS, influenza virus, and Borrelia burgdorferi. Production of polyreactive IgM during infection was Ag driven, not due to polyclonal B cell activation, as the majority of polyreactive IgM recognized ehrlichial Ag(s), including an immunodominant outer membrane protein. Monoclonal polyreactive IgM derived from T cell-independent spleen plasmablasts, which was germline-encoded, also bound cytoplasmic and nuclear Ags in HEp-2 cells. Polyreactive IgM protected immunocompromised mice against lethal bacterial challenge infection. Serum from human ehrlichiosis patients also contained polyreactive and self-reactive IgM. We propose that polyreactivity increases IgM efficacy during infection but may also exacerbate or mollify the response to foreign and self Ags.
Department of Biomedical Sciences, University at Albany, Albany, NY 12201, USA.
Derek D
DD
Jones
Gregory A
GA
DeIulio
Gary M
GM
Winslow
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage; D004536:Ehrlichia / Q000276:immunology; D016873:Ehrlichiosis / Q000097:blood / Q000276:immunology / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000942:Antigens, Bacterial; D000955:Antigens, T-Independent; D001425:Bacterial Outer Membrane Proteins; D016056:Immunodominant Epitopes; D007075:Immunoglobulin M