Abstract
Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation.
Highlights
Regulatory B cells (Bregs) contribute to immune regulation
CD11a, CD18, CD21, CD24, CD35, CD40, CD47, CD53, CD54, CD58, CD147, and integrin α4 expressions were higher on IL-10+ B cells than IL-10− B cells
Our data support that TIGIT+ memory B cells could represent human Bregs that are critical for immune regulation
Summary
Regulatory B cells (Bregs) contribute to immune regulation. the mechanisms of action of Bregs remain elusive. It has been difficult to know which subsets of human Bregs are more important than others for immune regulation, a critical question that needs to be addressed for the advancement of Breg biology and potential clinical development of Breg-based therapeutic strategy To address this critical question, it is essential to better define their surface phenotypes, as well as functional characteristics along with their mechanisms of action to suppress inflammatory responses. In this regard, we[15] previously reported that CD24hiCD27+ B10-like Bregs were more efficient than TBs at suppressing CD4+ T cell proliferation, as well as IFNγ/IL-17 expression in vitro. These prompted us to further investigate cellular and molecular phenotypes, as well as functional characteristics of human Bregs and Breg subsets
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