IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4
IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4
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DOI：
10.4049/jimmunol.181.3.1767
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发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Tangye, Stuart G.
中科院分区：
文献类型：
--
作者：
Avery, Danielle T.;Bryant, Vanessa L.;Tangye, Stuart G.
初始 B 细胞可以通过同种型转换来改变其 Ig 分子的效应功能，从而使它们不仅可以分泌 IgM，还可以分泌转换后的同种型 IgG、IgA 和 IgE。对特定病原体的反应会引发不同的同种型。同样，转换同种型的产生失调是多种疾病发生的基础，例如自身免疫和免疫缺陷。因此，表征控制同种型转换的介质及其对整体 B 细胞反应的贡献非常重要。 CD40L 与 IL-4、IL-10、IL-13 和/或 TGF-β 一起可诱导人初始 B 细胞中的同型转换。最近，IL-21 被确定为 IgG1 和 IgG3 的转换因子。然而，IL-21 对 IgA 转换的影响以及 IL-21 与其他转换因子之间的相互作用仍然未知。我们发现IL-4和IL-21分别诱导CD40L刺激的人初始B细胞转变为IgG，其中IL-4主要诱导IgG1(+)细胞，IL-21主要诱导IgG3。用 CD40L 和 IL-21（而不是 IL-4）培养初始 B 细胞也产生了 IgA(+) 细胞。 IL-4 和 IL-21 的组合对同种型转换具有不同的影响。具体来说，虽然IL-4和IL-21协同增加了CD40L刺激的B细胞产生IgG1(+)细胞，但IL-4同时消除了IL-21诱导的向IgA的转变。我们的研究结果证明了 IL-4 和 IL-21 在调节 IgG 亚类和 IgA 产生方面的动态相互作用，并表明这些细胞因子在针对特定病原体的不道德免疫反应中的暂时作用。
Naive B cells can alter the effector function of their Ig molecule by isotype switching, thereby allowing them to secrete not only IgM, but also the switched isotypes IgG, IgA, and IgE. Different isotypes are elicited in response to specific pathogens. Similarly, dysregulated production of switched isotypes underlies the development of various diseases, such as autoimmunity and immunodeficiency. Thus, it is important to characterize mediators controlling isotype switching, as well as their contribution to the overall B cell response. Isotype switching in human naive B cells can be induced by CD40L together with IL-4, IL-10, IL-13, and/or TGF-beta. Recently, IL-21 was identified as a switch factor for IgG1 and IgG3. However, the effect of IL-21 on switching to IgA, as well as the interplay between IL-21 and other switch factors, remains unknown. We found that IL-4 and IL-21 individually induced CD40L-stimulated human naive B cells to undergo switching to IgG, with IL-4 predominantly inducing IgG1(+) cells and IL-21 inducing IgG3. Culture of naive B cells with CD40L and IL-21, but not IL-4, also yielded IgA(+) cells. Combining IL-4 and IL-21 had divergent effects on isotype switching. Specifically, while IL-4 and IL-21 synergistically increased the generation of IgG1(+) cells from CD40L-stimulated B cells, IL-4 concomitantly abolished IL-21-induced switching to IgA. Our findings demonstrate the dynamic interplay between IL-4 and IL-21 in regulating the production of IgG subclasses and IgA, and suggest temporal roles for these cytokines in Immoral immune responses to specific pathogens.