Implication of TIGIT+ human memory B cells in immune regulation

Md Mahmudul Hasan, Sumi Sukumaran Nair, Jacqueline G. O’Leary, LuAnn Thompson-Snipes, Verah Nyarige, Junwen Wang, Walter Park, Mark Stegall, Raymond Heilman, Goran B. Klintmalm, HyeMee Joo () and SangKon Oh ()
Additional contact information
Md Mahmudul Hasan: Mayo Clinic
Sumi Sukumaran Nair: Mayo Clinic
Jacqueline G. O’Leary: Baylor University Medical Center
LuAnn Thompson-Snipes: Baylor University Medical Center
Verah Nyarige: Mayo Clinic
Junwen Wang: Mayo Clinic
Walter Park: Mayo Clinic
Mark Stegall: Mayo Clinic
Raymond Heilman: Mayo Clinic
Goran B. Klintmalm: Baylor University Medical Center
HyeMee Joo: Mayo Clinic
SangKon Oh: Mayo Clinic

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21413-y

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