Intestinal CD11b+ B Cells Ameliorate Colitis by Secreting Immunoglobulin A

Frontiers in Immunology

Yiwei Chu¹  Chujun Zhao²  Luman Wang³  Hongchun Liu⁴  Zhiming Wang⁵  Yuli Lin⁵  Ying Fu⁵  Wei Xu⁵  Mingfang Lu⁵  Ronghua Liu⁵  Baichao Yu⁵  Enyu Huang⁶  Yongzhong Liu⁷ 

[1] Biotherapy Research Center, Fudan University, Shanghai, China;Department of Biomedical Engineering, Columbia University, New York, NY, United States;Department of Endocrinology and Metabolism, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China;Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Immunology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China;Department of Pathology, The University of Hong Kong, Hong Kong, Hong Kong, SAR China;State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China;

关键词: CD11b+ B cells;    IgA;    DSS-induced colitis;    TGF-β;    Smad;   

DOI  :  10.3389/fimmu.2021.697725

来源: DOAJ

【 摘 要 】

The intestinal mucosal immune environment requires multiple immune cells to maintain homeostasis. Although intestinal B cells are among the most important immune cells, little is known about the mechanism that they employ to regulate immune homeostasis. In this study, we found that CD11b+ B cells significantly accumulated in the gut lamina propria and Peyer’s patches in dextran sulfate sodium-induced colitis mouse models and patients with ulcerative colitis. Adoptive transfer of CD11b+ B cells, but not CD11b−/− B cells, effectively ameliorated colitis and exhibited therapeutic effects. Furthermore, CD11b+ B cells were found to produce higher levels of IgA than CD11b− B cells. CD11b deficiency in B cells dampened IgA production, resulting in the loss of their ability to ameliorate colitis. Mechanistically, CD11b+ B cells expressed abundant TGF-β and TGF-β receptor II, as well as highly activate phosphorylated Smad2/3 signaling pathway, consequently promoting the class switch to IgA. Collectively, our findings demonstrate that CD11b+ B cells are essential intestinal suppressive immune cells and the primary source of intestinal IgA, which plays an indispensable role in maintaining intestinal homeostasis.

【 授权许可】

Unknown