Opposing roles of IgM and IgD in BCR-induced B-cell survival

被引:10
作者
Yasuda, Shoya [1 ,2 ]
Sun, Jiping [2 ]
Zhou, Yang [3 ,4 ]
Wang, Yanqing [4 ]
Lu, Qing [2 ]
Yamamura, Masayuki [1 ]
Wang, Ji-Yang [2 ,4 ]
机构
[1] Tokyo Inst Technol, Sch Comp, Yokohama, Kanagawa, Japan
[2] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai, Peoples R China
[3] Univ Sci & Technol China, Affiliated Hosp 1, Div Life Sci & Med, Dept Tradit Chinese Med, Hefei, Anhui, Peoples R China
[4] Fudan Univ, Inst Brain Sci, Sch Basic Med Sci,Collaborat Innovat Ctr Brain Sc, Dept Integrat Med & Neurobiol,State Key Lab Med N, Shanghai, Peoples R China
基金
日本学术振兴会; 中国国家自然科学基金;
关键词
IMMUNOGLOBULIN-D; IMMUNE-RESPONSES; APOPTOSIS INDUCTION; IN-VIVO; SURFACE; RECEPTOR; ANTIGEN; MICE; DIFFERENCE; SIGNALS;
D O I
10.1111/gtc.12635
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The B-cell receptor (BCR) transmits a tonic survival signal in the absence of antigen stimulation and an antigen-triggered survival signal. Mature B cells express two types of BCR, IgM and IgD, but it remains unclear how B-cell survival is differentially regulated by these two receptors. We found that, whereas cross-linking IgM on spleen B cells greatly enhanced their survival, cross-linking IgD did not enhance, but rather decreased, their survival. Consistently, cross-linking both IgM and IgD only moderately enhanced B-cell survival, suggesting that IgM and IgD play opposing roles in B-cell survival induced by BCR stimulation. Based on these and additional experimental results, we present a mathematical model integrating IgM- and IgD-mediated survival signals. Our model shows that IgD can transmit a tonic survival signal in the absence of antigen stimulation but cross-linking IgD not only does not generate a survival signal but also disrupts its tonic signal, resulting in inhibition of B-cell survival. These results suggest that IgD attenuates BCR-induced survival in mature B cells, presumably to restrain B-cell response to weak and/or self-antigens and prevent nonspecific B-cell activation and autoimmunity.
引用
收藏
页码:868 / 879
页数:12
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