Implication of TIGIT+ human memory B cells in immune regulation

Md Mahmudul Hasan; Sumi Sukumaran Nair; Jacqueline G. O’Leary; Lu Ann Thompson-Snipes; Verah Nyarige; Junwen Wang; Walter Park; Mark Stegall; Raymond Heilman; Goran B. Klintmalm; Hye Mee Joo; Sang Kon Oh

doi:10.1038/s41467-021-21413-y

Implication of TIGIT⁺ human memory B cells in immune regulation

Md Mahmudul Hasan, Sumi Sukumaran Nair, Jacqueline G. O’Leary, Lu Ann Thompson-Snipes, Verah Nyarige, Junwen Wang, Walter Park, Mark Stegall, Raymond Heilman, Goran B. Klintmalm, Hye Mee Joo, Sang Kon Oh

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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⁺CD24^hiCD27⁺CD39^hiIgD⁻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.

Original language	English (US)
Article number	1534
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21413-y
State	Published - Dec 1 2021
Externally published	Yes

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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title = "Implication of TIGIT+ human memory B cells in immune regulation",

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.",

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doi = "10.1038/s41467-021-21413-y",

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AU - Hasan, Md Mahmudul

AU - Nair, Sumi Sukumaran

AU - O’Leary, Jacqueline G.

AU - Thompson-Snipes, Lu Ann

AU - Nyarige, Verah

AU - Wang, Junwen

AU - Park, Walter

AU - Stegall, Mark

AU - Heilman, Raymond

AU - Klintmalm, Goran B.

AU - Joo, Hye Mee

AU - Oh, Sang Kon

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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Implication of TIGIT⁺ human memory B cells in immune regulation

Abstract

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