重组激活基因缺陷小鼠中抗DNA B细胞的调控

Xu H, Li H, Suri-Payer E, Hardy R R, Weigert M

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.

J Exp Med. 1998 Oct 5;188(7):1247-54. doi: 10.1084/jem.188.7.1247.

Anti-DNA antibodies are regulated in normal individuals but are found in high concentration in the serum of systemic lupus erythematosus (SLE) patients and the MRL lpr/lpr mouse model of SLE. We previously studied the regulation of anti-double-stranded (ds)DNA and anti-single-stranded (ss)DNA B cells in a nonautoimmune background by generating mice carrying immunoglobulin transgenes coding for anti-DNAs derived from MRL lpr/lpr. Anti-dsDNA B cells undergo receptor editing, but anti-ssDNA B cells seem to be functionally silenced. Here we have investigated how anti-DNA B cells are regulated in recombination- activating gene (RAG)-2-/- mice. In this setting, anti-dsDNA B cells are eliminated by apoptosis in the bone marrow and anti-ssDNA B cells are partially activated.

抗DNA抗体在正常个体中受到调控，但在系统性红斑狼疮（SLE）患者的血清以及SLE的MRL lpr/lpr小鼠模型中浓度很高。我们之前通过构建携带编码源自MRL lpr/lpr的抗DNA免疫球蛋白转基因的小鼠，研究了非自身免疫背景下抗双链（ds）DNA和抗单链（ss）DNA B细胞的调控情况。抗dsDNA B细胞会经历受体编辑，但抗ssDNA B细胞似乎在功能上处于沉默状态。在此，我们研究了重组激活基因（RAG）-2-/-小鼠中抗DNA B细胞是如何被调控的。在这种情况下，抗dsDNA B细胞在骨髓中通过凋亡被清除，而抗ssDNA B细胞则被部分激活。