POLYCLONAL-B CELL ACTIVATION IN LUPUS-PRONE MICE PRECEDES AND PREDICTS THE DEVELOPMENT OF AUTOIMMUNE-DISEASE
POLYCLONAL-B CELL ACTIVATION IN LUPUS-PRONE MICE PRECEDES AND PREDICTS THE DEVELOPMENT OF AUTOIMMUNE-DISEASE
复制标题
DOI：
10.1172/jci114831
复制
发表时间：
1990-10-01
影响因子：
15.9
通讯作者：
KLINMAN, DM
中科院分区：
文献类型：
--
作者：
KLINMAN, DM
多克隆B细胞活化是人类和小鼠系统性红斑狼疮自身免疫性疾病的早期特征。然而，多克隆激活对自身免疫进展的贡献尚不清楚，因为它先于终末器官损伤的发展数月或数年。为了研究这个问题，109名自身免疫易感者（NZB. NZW）F1 ×新西兰B回交小鼠在10周时半脾切除，其Ig分泌B细胞的数量和抗原特异性通过ELISA斑点试验进行定量。在61只具有多克隆增加的Ig分泌细胞/脾脏数量的小鼠中，31只在6个月前死亡。相反，在10周时Ig分泌B细胞数量正常的48只回交小鼠中0只在同一时期死亡（P < 0.001）。多克隆激活的小鼠也比同窝出生的Ig分泌细胞数量正常的小鼠更早和更频繁地发生蛋白尿（P < 0.001）。作为成年人，回交小鼠蛋白尿表达剧目倾向于生产抗DNA抗体。在第10周，这些小鼠表达了标记为多克隆活化而不是优先抗DNA产生的库。这些发现表明，SLE自身免疫性疾病伴随着自身抗原驱动的自身抗体的产生，但在多克隆B细胞活化之前和预测。
Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB .times. NZW)F1 .times. NZB backcross mice were hemi-splenectomized at 10 wk and the number and antigenic specificity of their Ig-secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P < 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P < 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti-DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation.