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.
|State||Published - 17 Dec 2019|
Bibliographical noteFunding Information:
We thank Dr. David Walker at the University of Texas Medical Branch for providing E. muris Ags Omp12 and Omp19. We thank the Histology Core at Magee Research Institute for laser micro-dissections. We are thankful to Laura Conter and Rachel Green for helping with the experiments. This work was funded by NIH grants NIH-1R01AI105018 and NIH-2R01AI043603 . A.M.R. was supported by NIH grant P01-AI106697 .
© 2019 Elsevier Inc.
- Ehrlichia muris
- age-associated B cells
- memory B cells
- somatic hypermutation
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases