Key Points Th17 cells promote intestinal memory IgA+ B cell development and IgA response. IL-21 is critical in regulating intestinal memory IgA+ B cell development. The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138−IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ−/− mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R−/− mice or IL-17R−/− mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer’s patches and LP was decreased only in IL-21R−/− mice, but not in IL-17R−/− mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium–specific IgA production as well as IgA+CD38+CD138− memory B cells in Peyer’s patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R−/− mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching–related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.

中文翻译：

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IL-21 促进肠道记忆 IgA 反应

关键点 Th17 细胞促进肠道记忆 IgA+ B 细胞发育和 IgA 反应。IL-21 在调节肠道记忆 IgA+ B 细胞发育中至关重要。IL-21 主要由 Th17 细胞和 T 滤泡辅助细胞产生，在 B 细胞分化和 Ab 类转换中的作用已得到深入研究。然而，IL-21 如何调节肠内记忆 IgA+B 细胞发育和记忆 IgA 反应仍不完全清楚。在本研究中，我们发现转移微生物群 Ag 特异性 Th17 细胞后 TCRβxδ−/− 小鼠肠固有层 (LP) 中的总 IgA+ B 细胞以及 CD38+CD138−IgA+ 记忆 B 细胞显着增加，而不是 Th1细胞。尽管 IL-21R-/- 小鼠或 IL-17R-/- 小鼠在被啮齿类柠檬酸杆菌感染后显示出肠道中 Ag 特异性记忆 IgA 的产生减少，与野生型相比，在啮齿类杆菌再感染后，派尔氏结节和 LP 中 IgA+CD38+CD138- 记忆 B 细胞的百分比仅在 IL-21R-/- 小鼠中降低，而在 IL-17R-/- 小鼠中没有降低型老鼠。体内阻断 IL-21 抑制了肠道啮齿类动物特异性 IgA 的产生以及派尔氏斑块和 LP 中的 IgA+CD38+CD138− 记忆 B 细胞。此外，IL-21 在体外显着诱导 B 细胞 IgA 产生，与类别转换和记忆 B 细胞发育相关的基因表达增加，包括 Aicda、Ski、Bmi1 和 Klf2。在 C.rodentium 再感染后，IL-21R-/- 小鼠的 B 细胞中的 Aicda 和 Ski 表达始终下降。总之，我们的研究表明 IL-21 促进肠道记忆 IgA B 细胞发育，