Intestinal CD11b+ B Cells Ameliorate Colitis by Secreting Immunoglobulin A.

Yongzhong Liu,Yiwei Chu,Enyu Huang,Zhiming Wang,Wei Xu,Baichao Yu,Mingfang Lu,Ronghua Liu,Hongchun Liu,Ying Fu,Luman Wang,Yuli Lin,Chujun Zhao

doi:10.3389/fimmu.2021.697725

Abstract

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.

Highlights

The intestine is a relatively independent regional immune organ, with bacteria, epithelial cells, and immune cells interacting to maintain homeostasis [1]
Our analysis confirmed that the proportion of Gut-associated lymphoid tissue (GALT) CD11b+ B cells in total lymphocytes increased (Supplementary Figures S1A, B), indicating that CD11b+ B cells were enriched in the GALT, in the colitis stage
We examined whether CD11b+B cells in LP and PP from day 0 to day 10 were the characteristic of memory B cells, plasmablasts, FIGURE 1 | CD11b is induced in Peyer’s patches (PPs) and colorectal lamina propria (LP) B cells during dextran sulfate sodium (DSS)-induced colitis

Summary

Introduction

The intestine is a relatively independent regional immune organ, with bacteria, epithelial cells, and immune cells interacting to maintain homeostasis [1]. Gut-associated lymphoid tissue (GALT) is an important site for resident immune cells to function as both a regulator and an effector [2]. Among the substances produced by immune cells, IgA is considered an essential factor in immune hemostasis [5,6,7]. CD11b activation promotes proinflammatory macrophage polarization and functions as a negative regulator of immune suppression as well as a target for cancer immune therapy [11]. Our previous work revealed that CD11b is expressed on classical B2 B cells, and CD11b+ B cells are essential for maintaining immune tolerance in the liver [16]. Whether CD11b+ B cells exist in GALT and whether the expression of CD11b in intestinal B cells determines the function of B cells in the maintenance of intestinal homeostasis are important questions that should be addressed

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