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

James J. Knox, Marcus Buggert, Lela Kardava, Kelly E. Seaton, Michael A. Eller, David H. Canaday, Merlin L. Robb, Mario A. Ostrowski, Steven G. Deeks, Mark K. Slifka, Georgia D. Tomaras, Susan Moir, M. Anthony Moody, Michael R. Betts

    Research output: Contribution to journalArticle

    47 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    JournalJCI Insight
    Volume2
    Issue number8
    DOIs
    StatePublished - Apr 20 2017

    Keywords

    • AIDS/HIV
    • Immunology

    ASJC Scopus subject areas

    • Medicine(all)

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    Knox, J. J., Buggert, M., Kardava, L., Seaton, K. E., Eller, M. A., Canaday, D. H., Robb, M. L., Ostrowski, M. A., Deeks, S. G., Slifka, M. K., Tomaras, G. D., Moir, S., Moody, M. A., & Betts, M. R. (2017). T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response. JCI Insight, 2(8). https://doi.org/10.1172/jci.insight.92943