Antigen-specific suppression of humoral immunity by anergic Ars/A1 B cells.

Antigen-specific suppression of humoral immunity by anergic Ars/A1 B cells.
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DOI:
10.4049/jimmunol.1201818
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发表时间:
2012-11-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Wysocki LJ
Wysocki LJ
中科院分区:
其他
文献类型:
--
作者:
Aviszus K;Macleod MK;Kirchenbaum GA;Detanico TO;Heiser RA;St Clair JB;Guo W;Wysocki LJ

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自身反应性无反应性B淋巴细胞被认为是危险的,因为它们有激活和招募进入自身免疫反应的潜力。然而,它们持续数天,并构成约5%的B细胞池。我们评估了它们在Ars/A1转基因模型中的功能潜力,其中无反应性B细胞表达双反应性抗原受体,除了自身抗原外,还结合半抗原对偶氮苯胂酸盐(Ars)。当Ars/A1 B细胞被转移到过继受体,免疫与Ars共价结合的外源蛋白,内源性IgG免疫反应都选择性和严重减少,和辅助性T细胞的发育受损。通过冗余机制,约4000个转移的Ars/A1 B细胞获得了约95%的抗Ars反应抑制,其中一种依赖于它们的MHC II表达,但不依赖于IL-10或IgM的分泌。这种抗原特异性抑制活性暗示自身反应性无反应性B细胞是对自身抗原的免疫耐受的执行者。
Autoreactive anergic B lymphocytes are considered to be dangerous because of their potential for activation and recruitment into autoimmune responses. Yet they persist for days and constitute ~5% of the B cell pool. We assessed their functional potential in the Ars/A1 transgene model, where anergic B cells express a dual-reactive antigen receptor that binds, in addition to a self-antigen, the hapten p-azophenylarsonate (Ars). When Ars/A1 B cells were transferred into adoptive recipients that were immunized with foreign proteins covalently conjugated with Ars, endogenous IgG immune responses to both were selectively and severely diminished, and the development of T helper cells was impaired. Approximately 95% inhibition of the anti-Ars response was attained with ~4000 transferred Ars/A1 B cells through redundant mechanisms, one of which depended upon their expression of MHC II but not upon secretion of IL-10 or IgM. This antigen-specific suppressive activity implicates the autoreactive anergic B cell as an enforcer of immunological tolerance to self-antigens.
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