B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation

被引:95
作者
Yan, Jun
Harvey, Bohdan P.
Gee, Renelle J.
Shlomchik, Mark J.
Mamula, Mark J.
机构
[1] Yale Univ, Sch Med, Rheumatol Sect, Dept Internal Med, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
关键词
D O I
10.4049/jimmunol.177.7.4481
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Both B cells and dendritic cells (DCs) have been implicated as autoantigen-presenting cells in the activation of self-reactive T cells. However, most self-proteins are ubiquitously and/or developmentally expressed, making it difficult to determine the source and the exposure of autoantigens to APCs in a controlled manner. In this study, we have used an Ig transgenic mouse model to examine the mechanisms by which B cells and other APCs acquire and present lupus autoantigens in vivo. Targeting a lupus autoantigen, the small nuclear ribonucleoprotein particle D protein, to the BCR activates autoreactive T cells in the periphery. Our in vivo studies demonstrate that autoantigen-specific B cells, when present in the repertoire, are the first subset of APCs to capture and present self-proteins for activating T cells. Thereafter, DCs acquire self-Ag and become effective APCs for stimulating the same subsets of autoreactive T cells. This mechanism provides one explanation of how early steps in autoimmunity can focus responses, via BCR, at a small group of self-proteins among the total milieu of intracellular self-proteins. Subsequently, DCs and other professional APCs may then amplify and perpetuate the autoimmune T cell response.
引用
收藏
页码:4481 / 4487
页数:7
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