Cutting edge: Low-affinity, Smith antigen-speciftic B cells are tolerized by dendritic cells and macrophages
Cutting edge: Low-affinity, Smith antigen-speciftic B cells are tolerized by dendritic cells and macrophages
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DOI：
10.4049/jimmunol.175.1.37
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Vilen, BJ
中科院分区：
文献类型：
--
作者：
Kilmon, MA;Rutan, JA;Vilen, BJ
多克隆 B 细胞激活可促进免疫力，且不会丧失耐受性。我们的数据表明，在先天免疫系统激活过程中，B 细胞对 Smith Ag Sm 的耐受性由树突状细胞 (DC) 和巨噬细胞 (M Phi) 维持。 TLR4激活的骨髓DC和M Phi，但不是浆细胞样或淋巴DC，通过分泌可溶性介质（包括IL-6）抑制自身反应性B细胞。虽然 IL-6 促进受到 Ag 急性刺激的 B 细胞的浆细胞分化，但我们发现它会抑制长期暴露于自身 Ag 的细胞。这种耐受机制不仅限于 Smith Ag 特异性 B 细胞，鸡蛋溶菌酶和对偶氮苯胂酸特异性 B 细胞也受到类似影响。我们的数据定义了 M Phi 和 DC 在先天免疫系统激活过程中调节自身反应性 B 细胞的耐受性作用。
Polyclonal B cell activation promotes immunity without the loss of tolerance. Our data show that during activation of the innate immune system, B cell tolerance to Smith Ag Sm is maintained by dendritic cells (DCs) and macrophages (M Phi). TLR4-activated myeloid DCs and M Phi, but not plasmacytoid or lymphoid DCs, repressed autoreactive B cells through the secretion of soluble mediators, including IL-6. Although IL-6 promotes plasma cell differentiation of B cells acutely stimulated by Ag, we show that it repressed cells that were chronically exposed to self-Ag. This mechanism of tolerance was not limited to Smith Ag-specific B cells as hen egg lysozyme- and p-azophenylarsonate-specific B cells were similarly affected. Our data define a tolerogenic rolefor M Phi and DCs in regulating autoreactive B cells during activation of the innate immune system.