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

Nikita Trivedi, Florian Weisel, Shuchi Smita, Stephen Joachim, Muhamuda Kader, Aditya Radhakrishnan, Chris Clouser, Aaron M. Rosenfeld, Maria Chikina, Francois Vigneault, Uri Hershberg, Nahed Ismail, Mark Jay Shlomchik

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1088-1101.e5
JournalImmunity
Volume51
Issue number6
DOIs
StatePublished - 17 Dec 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Ehrlichia muris
  • T-bet
  • age-associated B cells
  • liver
  • memory B cells
  • plasmablasts
  • somatic hypermutation

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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