Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers

Wenzhi Song, Olivia Q. Antao, Emily Condiff, Gina M. Sanchez, Irene Chernova, Krzysztof Zembrzuski, Holly Steach, Kira Rubtsova, Davide Angeletti, Alexander Lemenze, Brian J. Laidlaw, Joe Craft, Jason S. Weinstein

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Tbet+CD11c+ B cells arise during type 1 pathogen challenge, aging, and autoimmunity in mice and humans. Here, we examined the developmental requirements of this B cell subset. In acute infection, T follicular helper (Tfh) cells, but not Th1 cells, drove Tbet+CD11c+ B cell generation through proximal delivery of help. Tbet+CD11c+ B cells developed prior to germinal center (GC) formation, exhibiting phenotypic and transcriptional profiles distinct from GC B cells. Fate tracking revealed that most Tbet+CD11c+ B cells developed independently of GC entry and cell-intrinsic Bcl6 expression. Tbet+CD11c+ and GC B cells exhibited minimal repertoire overlap, indicating distinct developmental pathways. As the infection resolved, Tbet+CD11c+ B cells localized to the marginal zone where splenic retention depended on integrins LFA-1 and VLA-4, forming a competitive memory subset that contributed to antibody production and secondary GC seeding upon rechallenge. Therefore, Tbet+CD11c+ B cells comprise a GC-independent memory subset capable of rapid and robust recall responses.

Original languageEnglish
Pages (from-to)290-307.e5
JournalImmunity
Volume55
Issue number2
DOIs
StatePublished - Feb 8 2022

Keywords

  • TbetCD11c B cells
  • Tfh cells
  • age-associated B cells
  • germinal center
  • humoral memory

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