A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice.
A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice.
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DOI：
10.4049/jimmunol.160.1.51
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发表时间：
1998-01
影响因子：
4.4
通讯作者：
Owen Chan;M. Shlomchik
中科院分区：
文献类型：
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作者：
Owen Chan;M. Shlomchik
系统性红斑狼疮的发病机制的传统观点已经出现。B细胞的作用是分泌致病性自身抗体，而T细胞的作用是为产生自身抗体的B细胞提供帮助。这种观点的一个问题是，自发性T细胞活化以及器官如肾脏和皮肤的T细胞浸润是系统性红斑狼疮患者和狼疮鼠模型的突出特征。特别是T细胞浸润的鉴定表明，自身抗体介导的损伤可能只是故事的一部分，T细胞也可能在免疫介导的病理学中发挥主要作用。为了直接测试B细胞的作用，我们先前产生了缺乏B细胞的自身免疫易感MRL-lpr/lpr小鼠。这些小鼠中完全没有T细胞浸润是令人惊讶的，这促使我们研究B细胞在疾病演变中的关键作用是否是引发自身反应性T细胞。在这里，我们证明，通过比较B细胞缺陷和对照小鼠，在MRL-lpr/lpr小鼠的活化和记忆T细胞的扩增确实是高度依赖于B细胞。这些结果表明B细胞在自身免疫失调中发挥了新的作用。
A conventional view of the pathogenesis of systemic lupus erythematosus has emerged. The role of B cells is to secrete pathogenic autoantibodies, while the role of T cells is to provide help for autoantibody-producing B cells. A problem with this view is that spontaneous T cell activation as well as T cell infiltration of organs such as kidney and skin are prominent features in systemic lupus erythematosus patients and murine models of lupus. The identification of T cell infiltrates, in particular, suggests that autoantibody-mediated damage may be only part of the story and that T cells could also play a primary role in immune-mediated pathology. To test the role of B cells directly, we previously generated autoimmune-prone MRL-lpr/lpr mice that lack B cells. The complete absence of T cell infiltrates in these mice was surprising, and it prompted us to examine whether a key role of B cells in disease evolution is to prime autoreactive T cells. Here we demonstrate, by comparing B cell-deficient and control mice, that the expansion of activated and memory T cells in the MRL-lpr/lpr mouse is indeed highly dependent on B cells. These results suggest a novel role for B cells in autoimmune disregulation.