Early preplasma cells define a tolerance checkpoint for autoreactive B cells

被引:67
作者
Culton, DA [1 ]
O'Conner, BP [1 ]
Conway, KL [1 ]
Diz, R [1 ]
Rutan, J [1 ]
Vilen, BJ [1 ]
Clarke, SH [1 ]
机构
[1] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
关键词
D O I
10.4049/jimmunol.176.2.790
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ab-secreting plasma cells (PCs) are the effectors of Immoral immunity. In this study, we describe regulation of autoreactive B cells specific for the ribonucleoprotein Smith (Sm) at an early pre-PC stage. These cells are defined by the expression of the PC marker CD138 and normal levels of CD19 and B220. They are present at a high frequency in normal mouse spleen and bone marrow, are Ag dependent, and are located predominantly along the T cell-B cell border and near bridging channels. Anti-Sm pre-PCs also occur at a high frequency in nonautoimmume mice and show additional phenotypic characteristics of PC differentiation. However, while some of these pre-PCs are Ab-secreting cells, those specific for Sm are not, indicating regulation. Consistent with this, anti-Sm pre-PCs have a higher turnover rate and higher frequency of cell death than those that do not bind Sm. Regulation of anti-Sm pre-PCs occurs upstream of the transcriptional repressor, B lymphocyte-induced maturation protein-1, expression. Regulation at this stage is overcome in autoimmune MRL/lpr mice and is accompanied by an altered B lymphocyte stimulator receptor profile. These data reveal a new B cell tolerance checkpoint that is overcome in autoimmunity.
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收藏
页码:790 / 802
页数:13
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