Implication of TIGIT+ human memory B cells in immune regulation

• Published in: Nature communications 2021-03, Vol.12 (1), p.1534-1534, Article 1534
• Main Authors: Hasan, Md Mahmudul, Nair, Sumi Sukumaran, O’Leary, Jacqueline G., Thompson-Snipes, LuAnn, Nyarige, Verah, Wang, Junwen, Park, Walter, Stegall, Mark, Heilman, Raymond, Klintmalm, Goran B., Joo, HyeMee, Oh, SangKon
• Format: Article
• Language: English
• Subjects: 13; 13/31; 38; 38/91; 631/250/1619/40; 631/250/1854; 631/250/2520; 692/308/2778; Antibodies; Antigens, CD - metabolism; Antigens, CD1; Antigens, CD19; Apyrase - metabolism; Arresting (process); B-Lymphocytes - immunology; B-Lymphocytes, Regulatory - immunology; B7-H1 Antigen; CD19 antigen; CD1c antigen; CD24 Antigen - metabolism; CD73 antigen; CXCR5 protein; Dendritic cells; Glycoproteins; Granzyme B; Helper cells; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunoglobulin D; Immunoglobulin M; Immunological memory; Immunoreceptor tyrosine-based inhibition motif; Immunoregulation; Inducible T-Cell Co-Stimulator Protein; Inflammation; Interleukin 10; Liver transplantation; Lymphocytes; Lymphocytes B; Lymphocytes T; Memory cells; multidisciplinary; PD-L1 protein; Population; Receptors, CXCR5; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Science; Science (multidisciplinary); Th1 Cells; Th17 Cells - immunology; Th2 Cells; Transforming growth factor-b1; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21413-y

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 + CD24 hi CD27 + CD39 hi IgD − 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. Regulatory B cells have been shown to play critical roles in the modulation of the immune system. Here, the authors implicate TIGIT expression in B cells with the process of immuno-regulation.