Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206, USA.
J Immunol. 2012 Nov 1;189(9):4275-83. doi: 10.4049/jimmunol.1201818. Epub 2012 Sep 24.
Autoreactive anergic B lymphocytes are considered to be dangerous because of their potential for activation and recruitment into autoimmune responses. However, 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 Ag receptor that binds, in addition to a self-Ag, 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 on their expression of MHC class II but not upon secretion of IL-10 or IgM. This Ag-specific suppressive activity implicates the autoreactive anergic B cell as an enforcer of immunological tolerance to self-Ags.
自身反应性无应答 B 细胞被认为是危险的，因为它们有可能被激活并募集到自身免疫反应中。然而，它们可以持续数天，并构成 B 细胞池的约 5%。我们在 Ars/A1 转基因模型中评估了它们的功能潜力，在该模型中，无应答 B 细胞表达一种双重反应性 Ag 受体，除了自身 Ag 之外，还结合半抗原对氨基苯砷酸（Ars）。当 Ars/A1 B 细胞被转移到用 Ars 共价偶联的外源蛋白免疫的过继受体中时，对内源 IgG 对这两种抗原的免疫反应被选择性和严重地抑制，并且 T 辅助细胞的发育受到损害。通过冗余机制，大约 4000 个转移的 Ars/A1 B 细胞可以实现对 Ars 反应的约 95%抑制，其中一种机制依赖于它们 MHC 类 II 的表达，但不依赖于 IL-10 或 IgM 的分泌。这种 Ag 特异性抑制活性表明自身反应性无应答 B 细胞是自身抗原免疫耐受的执行者。
