Roark J H, Kuntz C L, Nguyen K A, Mandik L, Cattermole M, Erikson J
Wistar Institute, Philadelphia, PA 19104, USA.
J Immunol. 1995 May 1;154(9):4444-55.
We have used an Ig transgene (VH3H9) that increases the frequency of anti-DNA autoantibodies to address whether the production of antinuclear Abs in systemic lupus erythematosus is the consequence of a breakdown of B cell tolerance. We have shown that nonautoimmune mice regulate anti-DNA B cells, and that lupus-prone MRL-lpr/lpr mice are defective in this regulation. Here we show that a subset of anti-DNA B cells, namely those that stain nuclei in a homogeneous fashion, not only fail to be deleted in MRL-lpr/lpr mice, but undergo preferential clonal expansion. In addition, we describe a surprising finding: the VH3H9 transgene is less efficient at inhibiting endogenous heavy chain gene rearrangement on the autoimmune-prone MRL-lpr/lpr genetic background than on the nonautoimmune BALB/c background.
我们使用了一种能增加抗DNA自身抗体频率的Ig转基因（VH3H9），以探讨系统性红斑狼疮中抗核抗体的产生是否是B细胞耐受性破坏的结果。我们已经表明，非自身免疫小鼠能调节抗DNA B细胞，而倾向于患狼疮的MRL-lpr/lpr小鼠在这种调节方面存在缺陷。在此我们表明，抗DNA B细胞的一个亚群，即那些以均匀方式染色细胞核的细胞，不仅在MRL-lpr/lpr小鼠中未被清除，反而经历了优先的克隆扩增。此外，我们描述了一个惊人的发现：与非自身免疫的BALB/c背景相比，VH3H9转基因在自身免疫倾向的MRL-lpr/lpr遗传背景下抑制内源性重链基因重排的效率较低。
