B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation

Lisa G. Barnett, Helen M.A. Simkins, Burton E. Barnett, Lisa L. Korn, Andy L. Johnson, E. John Wherry, Gregory F. Wu, Terri M. Laufer

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

High-affinity class-switched Abs and memory B cells are products of the germinal center (GC). The CD4+ T cell help required for the development and maintenance of the GC is delivered by follicular Th cells (TFH), a CD4+ Th cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of TFH and GC B cells remain an important area of investigation. We previously showed that MHC class II (MHCII)-dependent dendritic cell Ag presentation is sufficient for the differentiation of a TFH intermediate (termed pre-TFH), characterized by Bcl-6 expression but lacking IL-21 secretion. In this article, we examine the contributions of MHCII Ag presentation by B cells to TFH differentiation and GC responses in several contexts. B cells alone do not efficiently prime naive CD4+ T cells or induce TFH after protein immunization; however, during lymphocytic choriomeningitis virus infection, B cells induce TFH differentiation despite the lack of effector CD4+ T cell generation. Still, MHCII+ dendritic cells and B cells cooperate for optimal TFH and GC B cell differentiation in response to both model Ags and viral infection. This study highlights the roles for B cells in both CD4+ T cell priming and TFH differentiation, and demonstrates that different APC subsets work in tandem to mediate the GC response.

Original languageEnglish
Pages (from-to)3607-3617
Number of pages11
JournalJournal of Immunology
Volume192
Issue number8
DOIs
StatePublished - Apr 15 2014

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