Liver Is a Generative Site for the B Cell Response to Ehrlichia muris

The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few—if any—germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet+ MBCs. T-bet+ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet+ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet+ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization. [Display omitted] •E. muris induces localized B cell proliferation, differentiation, and SHM in liver•Primary response and MBC clones interchange between liver and spleen•E. muris induces T-bet+ MBCs that adopt follicular, ABC, and MZ phenotypes•E. muris dissolves the MZ, which is subsequently reconstituted by T-bet+ MBCs Infection by the intracellular bacterium Ehrlichia induces few—if any—germinal centers, yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs). Trivedi et al. show that the liver and spleen are generative sites of B cell responses, including V-region mutation and long-term MBC localization, to E. muris.