The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell–expressed T-bet influence the host–pathogen balance during persisting infections is unclear. We demonstrate that B cell–specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virus-specific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.
This work was supported by National Institutes of Health Grants 1R56AI104898-01A1 (to J.T.), AI061699 (to S.L.R.), AI112521, AI105343, AI083022, and AI095608 (to E.J.W.), and AI082630 (to E.J.W. and G.M.L.).
The sequences presented in this article have been submitted to the National Center for Biotechnology Information Gene Expression Omnibus under accession number GSE81189.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- conditional Het, T-betflox/wtCD19cre
- conditional KO, T-betflox/floxCD19cre
- clone 13
- germinal center
- gene set enrichment analysis
- intestinal epithelial lymphocyte compartment
- lymphocytic choriomeningitis virus
- Received July 7, 2015.
- Accepted May 18, 2016.
- Copyright © 2016 by The American Association of Immunologists, Inc.