Chan O T, Hannum L G, Haberman A M, Madaio M P, Shlomchik M J
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Exp Med. 1999 May 17;189(10):1639-48. doi: 10.1084/jem.189.10.1639.
The precise role of B cells in systemic autoimmunity is incompletely understood. Although B cells are necessary for expression of disease (Chan, O., and M.J. Shlomchik. 1998. J. Immunol. 160:51-59, and Shlomchik, M.J., M.P. Madaio, D. Ni, M. Trounstine, and D. Huszar. 1994. J. Exp. Med. 180:1295-1306), it is unclear whether autoantibody production, antigen presentation, and/or other B cell functions are required for the complete pathologic phenotype. To address this issue, two experimental approaches were used. In the first, the individual contributions of circulating antibodies and B cells were analyzed using MRL/MpJ-Faslpr (MRL/lpr) mice that expressed a mutant transgene encoding surface immunoglobulin (Ig), but which did not permit the secretion of circulating Ig. These mice developed nephritis, characterized by cellular infiltration within the kidney, indicating that B cells themselves, without soluble autoantibody production, exert a pathogenic role. The results indicate that, independent of serum autoantibody, functional B cells expressing surface Ig are essential for disease expression, either by serving as antigen-presenting cells for antigen-specific, autoreactive T cells, or by contributing directly to local inflammation.
B细胞在全身性自身免疫中的精确作用尚未完全明确。尽管B细胞对于疾病的表达是必需的（Chan, O., 和M.J. Shlomchik. 1998. 《免疫学杂志》160:51 - 59，以及Shlomchik, M.J., M.P. Madaio, D. Ni, M. Trounstine, 和D. Huszar. 1994. 《实验医学杂志》180:1295 - 1306），但尚不清楚自身抗体产生、抗原呈递和/或其他B细胞功能对于完整的病理表型是否是必需的。为了解决这个问题，使用了两种实验方法。第一种方法是，利用表达编码表面免疫球蛋白（Ig）的突变转基因但不允许分泌循环Ig的MRL/MpJ - Faslpr（MRL/lpr）小鼠，分析循环抗体和B细胞各自的作用。这些小鼠发生了肾炎，其特征是肾脏内有细胞浸润，这表明B细胞本身在不产生可溶性自身抗体的情况下发挥致病作用。结果表明，独立于血清自身抗体，表达表面Ig的功能性B细胞对于疾病表达至关重要，其方式要么是作为抗原特异性自身反应性T细胞的抗原呈递细胞，要么是直接促成局部炎症。
