TY - JOUR AU - Knox, James J. AU - Buggert, Marcus AU - Kardava, Lela AU - Seaton, Kelly E. AU - Eller, Michael A. AU - Canaday, David H. AU - Robb, Merlin L. AU - Ostrowski, Mario A. AU - Deeks, Steven G. AU - Slifka, Mark K. AU - Tomaras, Georgia D. AU - Moir, Susan AU - Moody, M. Anthony AU - Betts, Michael R. T1 - T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response PY - 2017/04/20/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.92943 VL - 2 IS - 8 UR - https://doi.org/10.1172/jci.insight.92943 PB - The American Society for Clinical Investigation ER -