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

被引：136

作者：

Knox, James J. ^{[1
]}

Buggert, Marcus ^{[1
,2
]}

Kardava, Lela ^{[3
]}

Seaton, Kelly E. ^{[4
,5
]}

Eller, Michael A. ^{[6
,7
]}

Canaday, David H. ^{[8
,9
]}

Robb, Merlin L. ^{[6
,7
]}

Ostrowski, Mario A. ^{[10
,11
]}

Deeks, Steven G. ^{[12
]}

Slifka, Mark K. ^{[13
]}

Tomaras, Georgia D. ^{[4
,5
]}

Moir, Susan ^{[3
]}

Moody, M. Anthony ^{[14
,15
]}

Betts, Michael R. ^{[1
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[2] Karolinska Univ Hosp, Ctr Infect Med, Karolinska Inst, Dept Med, Huddinge, Stockholm, Sweden

[3] NIH, NIAID, Lab Immunoregulat, Bethesda, MD 20892 USA

[4] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA

[5] Duke Univ, Med Ctr, Dept Surg, Durham, NC USA

[6] US Mil, Walter Reed Army Inst Res, HIV Res Program, Silver Spring, MD 20910 USA

[7] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA

[8] Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA

[9] Cleveland VA, Cleveland, OH 44106 USA

[10] Univ Toronto, Dept Immunol & Med, Toronto, ON, Canada

[11] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada

[12] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[13] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR USA

[14] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Dept Pediat, Durham, NC USA

[15] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA

来源：

JCI INSIGHT | 2017年 / 2卷 / 08期

关键词：

HUMORAL IMMUNE-RESPONSES; T-BET EXPRESSION; MIXED CRYOGLOBULINEMIA; TRANSCRIPTION FACTOR; MEMORY; ANTIBODIES; POPULATION; CONTAIN; INNATE; COMPARTMENT;

D O I：

10.1172/jci.insight.92943

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：16

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