Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

被引：223

作者：

Chang, Pheh-Ping ^{[1
]}

Barral, Patricia ^{[2
]}

Fitch, Jessica ^{[1
]}

Pratama, Alvin ^{[1
]}

Ma, Cindy S. ^{[3
]}

Kallies, Axel ^{[4
]}

Hogan, Jennifer J. ^{[1
]}

Cerundolo, Vincenzo ^{[5
]}

Tangye, Stuart G. ^{[3
]}

Bittman, Robert ^{[6
]}

Nutt, Stephen L. ^{[4
]}

Brink, Robert ^{[3
]}

Godfrey, Dale I. ^{[7
]}

Batista, Facundo D. ^{[2
]}

Vinuesa, Carola G. ^{[1
]}

机构：

[1] Australian Natl Univ, John Curtin Sch Med Res, Dept Pathogens & Immun, Canberra, ACT 2601, Australia

[2] Canc Res UK, London Res Inst, Lymphocyte Interact Lab, London, England

[3] St Vincents Hosp, Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW 2010, Australia

[4] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[5] Univ Oxford, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England

[6] CUNY, Queens Coll, Dept Chem & Biochem, Flushing, NY USA

[7] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 01期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

KILLER T-CELLS; CYTOKINE PRODUCTION; ANTIBODY-RESPONSES; GERMINAL-CENTERS; ANTIGEN; COSTIMULATION; ACTIVATION; EXPANSION; PRECURSOR; SUBSETS;

D O I：

10.1038/ni.2166

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Lipid antigens trigger help from natural killer T cells (NKT cells) for B cells, and direct conjugation of lipid agonists to antigen profoundly augments antibody responses. Here we show that in vivo, NKT cells engaged in stable and prolonged cognate interactions with B cells and induced the formation of early germinal centers. Mouse and human NKT cells formed CXCR5(+)PD-1(hi) follicular helper NKT cells (NKTFH cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKTFH cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent germinal centers, those driven by NKTFH cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells.

引用

页码：35 / U56

页数：11

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