T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response.

Published online

Journal Article

Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection. Viremic HIV-infected individuals maintained a large T-bet+ B cell population during chronic infection that was associated with increased serum and cell-associated IgG1 and IgG3 expression. The HIV gp140-specific B cell response was dominated by T-bet-expressing memory B cells, and we observed a concomitant biasing of gp140-specific serum immunoglobulin to the IgG1 isotype. These findings suggest that T-bet induction promotes antiviral immunoglobulin isotype switching and development of a distinct T-bet+ B cell subset that is maintained by viremia and coordinates the HIV Env-specific humoral response.

Full Text

Duke Authors

Cited Authors

  • Knox, JJ; Buggert, M; Kardava, L; Seaton, KE; Eller, MA; Canaday, DH; Robb, ML; Ostrowski, MA; Deeks, SG; Slifka, MK; Tomaras, GD; Moir, S; Moody, MA; Betts, MR

Published Date

  • April 20, 2017

Published In

Volume / Issue

  • 2 / 8

PubMed ID

  • 28422752

Pubmed Central ID

  • 28422752

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.92943

Language

  • eng

Conference Location

  • United States