@article{fc8e3003355c4ee79c5f4c22e1a2a1e1,
title = "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.",
author = "Knox, {James J.} and Marcus Buggert and Lela Kardava and Seaton, {Kelly E.} and Eller, {Michael A.} and Canaday, {David H.} and Robb, {Merlin L.} and Ostrowski, {Mario A.} and Deeks, {Steven G.} and Slifka, {Mark K.} and Tomaras, {Georgia D.} and Susan Moir and Moody, {M. Anthony} and Betts, {Michael R.}",
note = "Funding Information: We would like to thank Lawrence C. Armand for production of the gp140-specific probes, Max C. Cooper for providing clone 2A6 antibody (anti-FcRL4/5), Shad Mosher and Judith Lucas for assistance with serum Ig isotype analyses, and E. John Wherry and Michael P. Cancro for productive discussions. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense. This work was supported by a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of Defense (DOD). Funding sources for this work include NIAID R01 AI076066 (MRB) and T32 AI007632 (JJK). The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2017 American Society for Clinical Investigation. All rights reserved.",
year = "2017",
month = apr,
day = "20",
doi = "10.1172/jci.insight.92943",
language = "English (US)",
volume = "2",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "8",
}