IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses
IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses
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DOI：
10.4049/jimmunol.165.8.4329
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发表时间：
2000-10-15
影响因子：
4.4
通讯作者：
Kiyono, H
中科院分区：
文献类型：
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作者：
Hiroi, T;Yanagita, M;Kiyono, H
我们在本报告中展示了 IL-15 和 IL-15R 在 B-1 细胞发育及其分化为 IgA 产生细胞中的新调节作用。研究发现，体内抗 IL-15 m4b 治疗可抑制粘膜 IgA 水平，但给予 rIL-15 可增强粘膜 IgA 水平，而血清 IgA 水平不受影响。体外，粘膜 B-1 细胞响应 IL-15 优先增殖。当将粘膜B-1和B-2细胞分成表面(s)IgM(+)sIgA(-)和sIgM(-)sIgA(+)部分时，发现IL-15R特异性mRNA在sIgM(+)sIgA(-)和sIgM(-)sIgA(+)B-1细胞中占主导地位，其水平比B-2细胞高得多。此外，与B-2级分相比，B-1和B-2细胞的这些不同子集与IL-15的温育导致B-1子集的相应受体表达的更大增强。有趣的是，从头分离出sIgM(+)sIgA(-) B-1，但不是sIgM(+)sIgA(-) B-2，细胞已经是类别转换细胞，因为检测到种系Ca转录本，然后通过IL-15进一步增强，IL-15还支持sIgM(+)sIgA(-)和sIgM(-)sIgA(+)的分化B-l细胞转变为产生IgA的细胞。总之，这些发现表明IL-15对于表达IL-15R的sIgM(+)、IgA(-)和sIgM(-)sIgA(+)B-1细胞分化成粘膜组织中的IgA产生细胞而言是极其重要的细胞因子。
We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-l cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 m4b treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-l cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-l and B-2 cells were separated into surface (s)IgM(+)sIgA(-) and sIgM(-)sIgA(+) fractions, IL-15R-specific mRNA was found to be predominant in both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-l cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-l and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-I subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM(+)sIgA(-) B-l, but not sIgM(+)sIgA(-) B-2, cells were already class-switched cells because the germline Ca transcript was detected and was then further enhanced by IL-15, IL-15 also supported differentiation of both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-l cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM(+),IgA(-) and sIgM(-)sIgA(+) B-l cells expressing IL-15R into IgA-producing cells in mucosal tissues.