Requirements for the natural killer cell-mediated induction of IgG1 and IgG2a expression in B lymphocytes
Requirements for the natural killer cell-mediated induction of IgG1 and IgG2a expression in B lymphocytes
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DOI：
10.1093/intimm/dxn021
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Yuan, Dorothy
中科院分区：
文献类型：
--
作者：
Gao, Ning;Jennings, Paula;Yuan, Dorothy
在与静息B淋巴细胞相互作用后，IL-2增殖的NK细胞可通过诱导γ 2a（I γ 2a）的生殖系转录物以及激活诱导的胞苷脱氨酶的mRNA水平增加来启动IG恒定区转换重组（CSR）过程。尽管这两个过程都是CSR所必需的，但它们是不够的，因为细胞不进行γ 2a（VDJC γ 2a）的成熟mRNA的表达。此外，NK细胞还可以上调B细胞中T盒转录因子（T-bet）的mRNA，而不能诱导进一步分化。使用对硝基苯酚（NP）具有B细胞受体特异性的转基因B细胞，我们现在已经表明，NP-Ficoll刺激的B细胞可以被NK细胞诱导表达IgG 2a以及IgG 1，推测是由于开关重组过程的完成。NK细胞的诱导能力不需要IFN-γ，但需要通过直接细胞接触经由CD 48传递的信号。此外，NP-Ficoll本身可诱导抗原特异性B细胞增殖以及γ 1的生殖系转录物;然而，VDJC γ 1 mRNA的表达还需要NK细胞与B淋巴细胞相互作用。因此，在抗原存在的情况下，NK细胞可以提供必要的信号，替代细胞因子诱导IgG 2a以及IgG 1表达。该体外分析为了解记录的NK细胞对体内T非依赖性B细胞应答的作用提供了机制基础。
Upon interaction with resting B lymphocytes, IL-2-propagated NK cells can initiate the process of Ig constant region switch recombination (CSR) by inducing germ line transcripts for gamma 2a (I gamma 2a) as well as increased levels of mRNA for activation-induced cytidine deaminase enzyme. Whereas both these processes are necessary for CSR, they are not sufficient because the cells do not proceed to the expression of mature mRNA for gamma 2a (VDJC gamma 2a). In addition, NK cells can also upregulate mRNA for the T-box transcription factor (T-bet) in B cells without being able to induce further differentiation. Using transgenic B cells with B cell receptor specificity for nitrophenol (NP), we have now shown that NP-Ficoll-stimulated B cells can be induced by NK cells to express IgG2a as well as IgG1 presumably due to the completion of the process of switch recombination. The inductive ability of NK cells does not require IFN-gamma but does require signals transmitted via CD48 by direct cell contact. In addition, NP-Ficoll on its own can induce proliferation of antigen-specific B cells as well as germ line transcripts of gamma 1; however, expression of VDJC gamma 1 mRNA also requires NK cell interaction with B lymphocytes. Therefore, in the presence of antigen, NK cells can provide a necessary signal that substitutes for cytokines in the induction of IgG2a as well as IgG1 expression. This in vitro analysis provides a mechanistic basis for understanding the documented NK cell effects on T-independent B cell responses in vivo.