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

Immunity. 2022 Feb 8;55(2):290-307.e5. doi: 10.1016/j.immuni.2022.01.002. Epub 2022 Jan 31.


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.

Keywords: Tbet(+)CD11c(+) B cells; Tfh cells; age-associated B cells; germinal center; humoral memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD11 Antigens / metabolism*
  • Cell Differentiation / immunology
  • Germinal Center / immunology
  • Influenzavirus A / immunology
  • Integrins / metabolism
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocytic choriomeningitis virus / immunology
  • Memory B Cells / immunology
  • Memory B Cells / metabolism
  • Mice
  • Spleen / immunology
  • T Follicular Helper Cells / immunology*
  • T-Box Domain Proteins / metabolism*
  • Virus Diseases / immunology*


  • Antibodies, Viral
  • CD11 Antigens
  • Integrins
  • Itgax protein, mouse
  • T-Box Domain Proteins