Shinde S, Gee R, Santulli-Marotto S, Bockenstedt L K, Clarke S H, Mamula M J
Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 1999 Jun 15;162(12):7519-24.
Autoantibodies directed at a diverse group of proteins of the U1/Sm ribonucleoprotein (snRNP) are characteristic of systemic lupus erythematosus and are found in the MRL murine model of this disease. This study examines the role of transgenic B lymphocytes in the regulation of autoreactive T cells to the snRNP autoantigen. Transgenic mice were developed bearing an Ig heavy chain gene specific for the D protein component of murine snRNP. B lymphocytes in these mice are neither deleted nor anergic and are of an immature (heat-stable Aghigh) phenotype. T lymphocytes from anti-snRNP transgenic mice were examined using a recombinant form of the D protein of the murine snRNP complex. Our results revealed that transgenic anti-snRNP B cell APCs stimulated CD4 T cells from wild-type C57BL/6 and MRL lpr/lpr mice, while nonspecific APCs failed to stimulate CD4 T cells. This study demonstrates that autoreactive T cells are not deleted from wild-type mice, although their activation is facilitated by autoantigen-specific APCs. The snRNP-reactive T cells in C57BL/6 transgenic mice are tolerized, in contrast to those T cells from MRL lpr/lpr transgenic mice. These studies implicate a role for autoreactive B lymphocytes in the in vivo activation and/or diversification of autoreactive T cells.
针对U1/Sm核糖核蛋白（snRNP）多种蛋白质的自身抗体是系统性红斑狼疮的特征，并且在该疾病的MRL小鼠模型中也可发现。本研究探讨了转基因B淋巴细胞在调节针对snRNP自身抗原的自身反应性T细胞中的作用。构建了携带针对小鼠snRNP的D蛋白成分的Ig重链基因的转基因小鼠。这些小鼠中的B淋巴细胞既未被清除也无反应迟钝，且呈现未成熟（热稳定Aghigh）表型。使用小鼠snRNP复合物D蛋白的重组形式检测抗snRNP转基因小鼠的T淋巴细胞。我们的结果显示，转基因抗snRNP B细胞抗原呈递细胞（APC）刺激野生型C57BL/6和MRL lpr/lpr小鼠的CD4 T细胞，而非特异性APC则无法刺激CD4 T细胞。本研究表明，自身反应性T细胞在野生型小鼠中未被清除，尽管其激活由自身抗原特异性APC促进。与来自MRL lpr/lpr转基因小鼠的T细胞相反，C57BL/6转基因小鼠中对snRNP有反应的T细胞处于耐受状态。这些研究表明自身反应性B淋巴细胞在自身反应性T细胞的体内激活和/或多样化中发挥作用。
