Tolerance Induction of IgG+ Memory B Cells by T Cell-Independent Type II Antigens
Tolerance Induction of IgG+ Memory B Cells by T Cell-Independent Type II Antigens
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DOI：
10.4049/jimmunol.1100213
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发表时间：
2011-05-15
影响因子：
4.4
通讯作者：
Kitamura, Daisuke
中科院分区：
文献类型：
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作者：
Haniuda, Kei;Nojima, Takuya;Kitamura, Daisuke
在T细胞依赖的免疫反应中产生的记忆B细胞通过产生大量的以高亲和力结合同源抗原的抗体来对二次免疫迅速做出反应。目前尚不清楚记忆B细胞的这种高回忆反应是否是由于增强的Ig G-BCR信号，这只在幼稚的转基因B细胞的背景下被证明。为了解决这个问题，我们研究了记忆B细胞是否可以在体内对仅通过BCR刺激的AGS做出反应，即T细胞非依赖型II(TI-II)AGS。在这项研究中，我们发现TI-II Ag(4-羟基-3-硝基苯基)乙酰基(NP)-Ficoll不能在T细胞依赖的Ag-NP-鸡丙种球蛋白免疫的小鼠中引起召回反应。此外，体内和体外的NP-Ficoll挑战以B细胞固有的方式显著抑制了随后对NP-鸡丙种球蛋白的回忆反应。这种NP-Ficoll介导的耐受是由于优先消除与NP高亲和力结合的免疫球蛋白G(+)记忆B细胞所致。这些数据表明，BCR与TI-II抗原的交联不会激活免疫球蛋白G(+)的记忆B细胞，而是耐受它们，识别记忆B细胞分化的终端检查点，这可能会阻止自身免疫。免疫学杂志，2011,186：5620-5628。
Memory B cells generated during a T cell-dependent immune response rapidly respond to a secondary immunization by producing abundant IgG Abs that bind cognate Ag with high affinity. It is currently unclear whether this heightened recall response by memory B cells is due to augmented IgG-BCR signaling, which has only been demonstrated in the context of naive transgenic B cells. To address this question, we examined whether memory B cells can respond in vivo to Ags that stimulate only through BCR, namely T cell-independent type II (TI-II) Ags. In this study, we show that the TI-II Ag (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll cannot elicit the recall response in mice first immunized with the T cell-dependent Ag NP-chicken gamma-globulin. Moreover, the NP-Ficoll challenge in vivo as well as in vitro significantly inhibits a subsequent recall response to NP-chicken gamma-globulin in a B cell-intrinsic manner. This NP-Ficoll-mediated tolerance is caused by the preferential elimination of IgG(+) memory B cells binding to NP with high affinity. These data indicate that BCR cross-linking with a TI-II Ag does not activate IgG(+) memory B cells, but rather tolerizes them, identifying a terminal checkpoint of memory B cell differentiation that may prevent autoimmunity. The Journal of Immunology, 2011, 186: 5620-5628.