Liver is a generative site for the B cell response to Ehrlichia muris

Murine infection with Ehrlichia muris models human Ehrlichiosis, with prominent liver involvement. The B cell response is dominated by plasmablasts (PBs), with few germinal centers (GC), yet it generates protective IgM memory B cells (MBC) that express T-bet and harbor V region mutations. Here we address the origins, specificity, and locations of these responses. B cells within infected livers were proliferating and undergoing somatic hypermutation (SHM). Vh region sequencing revealed trafficking of B cell clones between the spleen and liver that was often followed by localized clonal expansion. A subset of T-bet+ MBCs persisted in livers after infection. These cells resisted intravascular labeling and were observed at intraparenchymal locations. Hence, liver can be a generative site of B cell responses that include V region mutation, MBC generation, and long-term MBC localization. Further, T-bet+ MBC expressed diverse surface phenotypes and colonized the splenic marginal zone, revealing unexpected plasticity of T-bet+ MBC.