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Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice.他莫昔芬可减轻自身免疫性MRL-lpr/lpr小鼠的疾病严重程度并减少双阴性T细胞。
Immunology. 2000 May;100(1):110-8. doi: 10.1046/j.1365-2567.2000.00998.x.

自身免疫性NZB×NZW F1小鼠CD5+和CD5- B细胞的体外和体内功能分析

In vitro and in vivo functional analysis of CD5+ and CD5- B cells of autoimmune NZB x NZW F1 mice.

作者信息

Ye Y L, Chuang Y H, Chiang B L

机构信息

Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, R.O.C.

出版信息

Clin Exp Immunol. 1996 Nov;106(2):253-8. doi: 10.1046/j.1365-2249.1996.d01-840.x.

DOI:10.1046/j.1365-2249.1996.d01-840.x
PMID:8918570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2200577/
Abstract

Polyclonal B cell activation has been thought to play the critical role in production of autoantibodies, and possible activation of autoreactive T cells in murine lupus, especially abnormal expansion of CD5+ B cells, is one of the characteristic findings in these mice. The aim of this study was to investigate further the characteristics and function of CD5+ and CD5- B cells. Both CD5+ and CD5- B cells were isolated for in vitro autoantibody production, cytokine expression and in vivo anti-DNA antibody production with reconstitution of severe combined immunodeficient (SCID) mice. The data showed: (i) both CD5+ and CD5- B cells produced a high level of anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5; (ii) both peritoneal CD5+ and CD5- B cells expressed a high level of IL-10 mRNA after stimulation with LPS, while in contrast CD5- B cells of non-autoimmune BALB/c mice did not express IL-10 mRNA after stimulation; (iii) SCID mice reconstituted with either CD5+ or CD5- B cells all produced significant levels of anti-DNA antibodies in vivo and manifested with proteinuria. These data suggest both CD5+ and CD5- B cells play important roles in polyclonal B cell activation and subsequent autoantibody production. Generalized polyclonal B cell activation, instead of expanding a certain subpopulation of B cells, contributed to the pathogenesis of autoimmunity in murine lupus.

摘要

多克隆B细胞激活被认为在自身抗体产生中起关键作用，并且在小鼠狼疮中自身反应性T细胞的可能激活，尤其是CD5+B细胞的异常扩增，是这些小鼠的特征性发现之一。本研究的目的是进一步研究CD5+和CD5-B细胞的特征和功能。分离出CD5+和CD5-B细胞用于体外自身抗体产生、细胞因子表达以及在重度联合免疫缺陷（SCID）小鼠重建后的体内抗DNA抗体产生实验。数据显示：（i）用脂多糖（LPS）加IL-5刺激后，CD5+和CD5-B细胞均产生高水平的抗DNA抗体；（ii）用LPS刺激后，腹膜内的CD5+和CD5-B细胞均高水平表达IL-10 mRNA，而相比之下，非自身免疫性BALB/c小鼠的CD5-B细胞在刺激后不表达IL-10 mRNA；（iii）用CD5+或CD5-B细胞重建的SCID小鼠在体内均产生显著水平的抗DNA抗体并出现蛋白尿。这些数据表明CD5+和CD5-B细胞在多克隆B细胞激活及随后的自身抗体产生中均起重要作用。全身性多克隆B细胞激活，而非特定B细胞亚群的扩增，促成了小鼠狼疮自身免疫的发病机制。