Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice interact to generate IgM and IgG autoantibodies.
Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice interact to generate IgM and IgG autoantibodies.
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自然杀伤 T 细胞和来自狼疮易发性 NZB/W 小鼠的先天免疫 B 细胞相互作用，产生 IgM 和 IgG 自身抗体。
DOI：
10.1002/eji.200737656
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发表时间：
2008
影响因子：
5.4
通讯作者：
Strober,Samuel
中科院分区：
文献类型：
--
作者：
Takahashi,Tsuyoshi;Strober,Samuel
大约6个月大时，狼疮易感NZB/WF 1小鼠在T辅助细胞依赖性同种型将自身抗体分泌从IgM转换为IgG后发生肾小球肾炎。 我们比较了先天免疫自然杀伤（NK）T细胞和常规T细胞帮助NZ B/W F1小鼠先天免疫（B-1和边缘区）和常规（滤泡）B细胞亚群自发分泌体外免疫球蛋白和自身抗体的能力。我们发现，纯化的NKT细胞不仅增加了B-1和边缘区B细胞自发分泌IgM和IgM抗双链（ds）DNA抗体，而且还促进了主要由B-1 B细胞分泌IgG抗dsDNA抗体。滤泡B细胞分泌的IgM或IgG抗dsDNA抗体很少，常规T细胞不能为任何B细胞亚群提供有效的辅助活性。来自正常C57 BL/6小鼠的T和B细胞亚群的所有组合都不能产生剧烈的IgM和IgG分泌。NZB/W NKT辅助细胞活性被抗CD 1和抗CD 40 L mAb阻断。总之，先天免疫T和B细胞之间的直接相互作用形成了新西兰B/W小鼠中IgM和IgG狼疮自身抗体分泌的发展途径。
Lupus‐prone NZB/W F1 mice develop glomerulonephritis after T helper cell‐dependent isotype switching of autoantibody secretion from IgM to IgG at about 6 months of age. We compared innate immune natural killer (NK) T cells and conventional T cells for their capacity to help spontaneousin vitroimmunoglobulin and autoantibody secretion of innate immune (B‐1 and marginal zone) and conventional (follicular) B cell subsets from NZB/W F1 mice. We found that purified NKT cells not only increased spontaneous secretion of IgM and IgM anti‐double‐stranded (ds)DNA antibodies by B‐1 and marginal zone B cells, but also facilitated secretion of IgG anti‐dsDNA antibodies predominantly by B‐1 B cells. Few IgM or IgG anti‐dsDNA antibodies were secreted by follicular B cells, and conventional T cells failed to provide potent helper activity to any B cell subset. All combinations of T and B cell subsets from normal C57BL/6 mice failed to generate vigorous IgM and IgG secretion. NZB/W NKT cell helper activity was blocked by anti‐CD1 and anti‐CD40L mAb. In conclusion, direct interactions between innate immune T and B cells form a pathway for the development of IgM and IgG lupus autoantibody secretion in NZB/W mice.