Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner

被引:171
作者
King, Irah L. [1 ]
Fortier, Anne [1 ]
Tighe, Michael [1 ]
Dibble, John [1 ]
Watts, Gerald F. M. [2 ]
Veerapen, Natacha [3 ]
Haberman, Ann M. [4 ]
Besra, Gurdyal S. [3 ]
Mohrs, Markus [1 ]
Brenner, Michael B. [2 ]
Leadbetter, Elizabeth A. [1 ]
机构
[1] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol, Boston, MA 02115 USA
[3] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England
[4] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA
基金
英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会;
关键词
CXC CHEMOKINE RECEPTOR-5; MARGINAL ZONE; NKT CELLS; ANTIBODY-RESPONSES; CUTTING EDGE; IN-VIVO; IMMUNOGLOBULIN; IL-21; DIFFERENTIATION; ACTIVATION;
D O I
10.1038/ni.2172
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mouse invariant natural killer T cells (iNKT cells) provide cognate and noncognate help for lipid and protein-specific B cells, respectively. However, the long-term outcome for B cells after cognate help is provided by iNKT cells is unknown at present. Here we found that cognate iNKT cell help resulted in a B cell differentiation program characterized by extrafollicular plasmablasts, germinal-center formation, affinity maturation and a robust primary immunoglobulin G (IgG) antibody response that was uniquely dependent on iNKT cell-derived interleukin 21 (IL-21). However, cognate help from iNKT cells did not generate an enhanced humoral memory response. Thus, cognate iNKT cell help for lipid-specific B cells induces a unique signature that is a hybrid of classic T cell-dependent and T cell-independent type 2 B cell responses.
引用
收藏
页码:44 / U64
页数:8
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