Novel suppressive function of transitional 2 B cells in experimental arthritis
Novel suppressive function of transitional 2 B cells in experimental arthritis
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DOI：
10.4049/jimmunol.178.12.7868
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发表时间：
2007-06-15
影响因子：
4.4
通讯作者：
Mauri, Claudia
中科院分区：
文献类型：
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作者：
Evans, Jamie G.;Chavez-Rueda, Karina A.;Mauri, Claudia
免疫系统包含在维持耐受性中重要的天然调节细胞。尽管这种抑制功能通常归因于CD 4调节性T细胞，但最近的报道揭示了IL-10产生性B细胞在包括胶原诱导的关节炎在内的几种自身免疫性疾病中的免疫调节作用。在本研究中，我们将这种抑制功能归因于表达高水平的CD 21、CD 23和IgM的B细胞亚群，该亚群先前被鉴定为过渡性2-边缘区前体（T2-MZP）B细胞。T2-MZP B细胞存在于幼稚小鼠的脾脏中，并在关节炎缓解期增加。过继转移到免疫的DBA/1小鼠后，T2-MZP B细胞显著预防新的疾病并改善已建立的疾病。对关节炎的抑制作用通过抑制Ag特异性T细胞活化和减少表现出Th 1型功能应答的细胞来实现。我们还提供了证据表明，这一调节子集介导其抑制通过分泌抑制性细胞因子，而不是通过细胞与细胞接触。通过T2-MZP B细胞调节已建立的免疫应答的能力赋予该B细胞亚群显著的且先前未被认识的免疫调节潜力。
The immune system contains natural regulatory cells important in the maintenance of tolerance. Although this suppressive function is usually attributed to CD4 regulatory T cells, recent reports have revealed an immunoregulatory role for IL-10-producing B cells in the context of several autoimmune diseases including collagen-induced arthritis. In the present study, we attribute this suppressive function to a B cell subset expressing high levels of CD21, CD23, and IgM, previously identified as transitional 2-marginal zone precursor (T2-MZP) B cells. T2-MZP B cells are present in the spleens of naive mice and increase during the remission phase of arthritis. Following adoptive transfer to immunized DBA/1 mice, T2-MZP B cells significantly prevented new disease and ameliorated established disease. The suppressive effect on arthritis was paralleled by an inhibition of Ag-specific T cell activation and a reduction in cells exhibiting Thl-type functional responses. We also provide evidence that this regulatory subset mediates its suppression through the secretion of suppressive cytokines and not by cell-to-cell contact. The ability to regulate an established immune response by T2-MZP B cells endows this subset of B cells with a striking and previously unrecognized immunoregulatory potential.