Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo.
Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo.
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DOI：
10.1084/jem.20091873
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发表时间：
2010-01-18
期刊：
影响因子：
--
通讯作者：
Nemazee D
中科院分区：
文献类型：
--
作者：
Duong BH;Tian H;Ota T;Completo G;Han S;Vela JL;Ota M;Kubitz M;Bovin N;Paulson JC;Nemazee D
自身反应性 B 淋巴细胞首先在外周组织中遇到自身抗原，通常通过诱导无反应性或凋亡来调节。根据“双信号”模型，除非提供 T 细胞帮助或脂多糖等炎症信号，否则仅靠抗原识别就可以使 B 细胞产生耐受。然而，对于 T 依赖性 2 型 (TI-2) 抗原的反应似乎不需要此类信号，TI-2 抗原是缺乏 T 细胞表位和 Toll 样受体配体的多聚体抗原。那么成熟的 B 细胞如何避免对多聚体自身抗原产生类似 TI-2 的反应呢？我们提供的证据表明，用抑制性唾液酸结合 Ig 样凝集素 (siglecs) 配体修饰的 TI-2 抗原的免疫原性较差，并且可以诱导对随后免疫原性抗原攻击的耐受性。两种 siglec，CD22 和 Siglec-G，有助于诱导耐受性，防止浆细胞分化或存活。尽管 CD22 及其信号机制的突变与 B 细胞发育和自身抗体产生失调有关，但之前的分析未能识别抗原特异性突变 B 细胞的耐受缺陷。我们的结果支持 siglecs 在 B 细胞自我/非自我歧视中的作用，即抑制对自身相关抗原的反应，同时允许对非唾液酸化多聚体抗原的快速“缺失自我”反应。结果表明使用 siglec 配体抗原构建体作为诱导耐受的方法。
Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the “two-signal” model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2–like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid–binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid “missing self”–responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance.
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DOI：
10.1073/pnas.73.10.3671
发表时间：
1976-01-01
影响因子：
11.1
作者：
DINTZIS, HM;DINTZIS, RZ;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1073/pnas.0400851101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Collins, BE;Blixt, O;Paulson, JC
通讯作者：
Paulson, JC
影响因子：
32.4
作者：
Alugupalli, KR;Leong, JM;Gerstein, RM
通讯作者：
Gerstein, RM
影响因子：
32.4
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
通讯作者：
Goodnow, CC
DOI：
10.1126/science.1168988
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen GY;Tang J;Zheng P;Liu Y
通讯作者：
Liu Y