T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response
James J. Knox, … , M. Anthony Moody, Michael R. Betts
James J. Knox, … , M. Anthony Moody, Michael R. Betts
Published April 20, 2017
Citation Information: JCI Insight. 2017;2(8):e92943. https://doi.org/10.1172/jci.insight.92943.
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Research Article AIDS/HIV Immunology

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

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.

Authors

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

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Figure 5

gp140-specific memory B cell phenotypes and serum Ig isotypes.

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gp140-specific memory B cell phenotypes and serum Ig isotypes. (A) gp140...
(A) gp140-specific serum Ig titers by isotype from progressors (n = 10). Titers were normalized using age/ethnicity–matched controls. Statistical comparison calculated using repeated-measures 1-way ANOVA with Tukey’s multiple comparisons test. (B) Representative staining of gp140-specific class-switched (IgD–IgM–) memory B cells from a progressor. (C) Frequency of gp140-specific cells within total class-switched memory B cells by cohort. n = 10 for all cohorts except progressors (n = 11). (D) T-bet expression of gp140-specific B cells (red) and total B cells (black) from a representative progressor. (E) Frequency of T-bet expression within gp140-specific cells from HIV+ cohorts (n = 10 progressors, n = 10 viremic controllers [VC], n = 6 elite controllers [EC]). All donors with less than 40 gp140-specific cells (including all antiretroviral therapy [ART] individuals) were excluded from analyses in E and F. No statistical differences were observed between donor groups. (F) Frequency of gp140-specific cells with T-bethiCD85jhi phenotype by cohort. For C, E, and F, statistical comparisons were calculated using 1-way ANOVA with Tukey’s multiple comparisons test. *P ≥ 0.01 to < 0.05; **P ≥ 0.001 to < 0.01; ***P < 0.001.