IL-21 Promotes Intestinal Memory IgA Responses

• Published in: The Journal of immunology (1950) Vol. 205; no. 7; pp. 1944 - 1952
• Main Authors: Huang, Xiangsheng, Yang, Wenjing, Yao, Suxia, Bilotta, Anthony J, Lu, Yao, Zhou, Zheng, Kumar, Pawan, Dann, Sara M, Cong, Yingzi
• Format: Journal Article
• Language: English
• Published: United States 01.10.2020
• Subjects: Animals; B-Lymphocytes - immunology; Cells, Cultured; Citrobacter rodentium - physiology; Enterobacteriaceae Infections - immunology; Immunoglobulin A - metabolism; Immunoglobulin Class Switching - genetics; Immunologic Memory; Interleukins - metabolism; Intestinal Mucosa - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin-21 - genetics; Receptors, Interleukin-21 - metabolism; Th17 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1900766

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 , 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 compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal -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 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.