Induction of a polyreactive IgM response by bacterial infection (99.26)

Abstract

Abstract Infection of mice with the bacterium Ehrlichia muris induces a protective T cell-independent (TI) IgM response. A unique property of the TI IgM produced during early infection is that it is polyreactive; that is, it binds a number of unrelated foreign and self antigens, including influenza virus, Borrelia burgdorferi, ss- and dsDNA, insulin, and thyroglobulin. We hypothesized that polyreactivity results from cross-reactivity of antigen-specific IgM, or that antibodies of unrelated specificity were generated via polyclonal B cell activation. To address these hypotheses, we generated B cell hybridomas from infected spleen cells and determined whether they produced pathogen-specific IgM. Eighty percent of the IgM-producing hybridomas were ehrlichia-specific; 10% of the IgM bound an immunodominant ehrlichial antigen, OMP-19, and the remainder bound yet unidentified ehrlichial antigen(s). Polyreactivity was exclusively associated with OMP-19-specific IgM, however, indicating that the properties of the antigen (e.g., spatial distribution on the bacterium) influence the selection of polyreactive IgM. These data indicate that polyreactive IgM is generated by antigen-specific B cells. Our data support a model whereby polyreactivity among antigen-specific IgM allows for the heteroligation (Mouquet et al., 2010) of OMP-19 and additional ehrlichial antigens, and serves to increase the relative affinity of IgM.