1. ICAM-1 mediated cell-cell adhesion exerts dual roles on human B cell differentiation and IgG production
- Author
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Shuai Liu, Zhi-cui Liu, Mei-yu Zhang, Shu-jun Wang, Meng Pan, Ping Ji, Cheng Zhu, Ping Lin, and Ying Wang
- Subjects
Molecular biology ,Immunology ,Components of the immune system ,Cell biology ,Cancer ,Science - Abstract
Summary: Intercellular adhesion molecule 1 (ICAM-1) plays prominent roles in mediating cell-cell adhesion which also facilitates B cell activation and differentiation with the help from CD4+ T cells. Here, we have reported a unique phenomenon that increased ICAM-1 on purified human CD4+ T cells upon anti-CD3/CD28 stimulation enhanced CD4+ T-B cell adhesion whereas induced less B cell differentiation and IgG production. This was largely due to increased PD-1 expression on CD19hi B cells after coculturing with hyperactivated CD4+ T cells. Consequently, ICAM-1 blockade during CD4+ T cell-B cell coculture promoted IgG production with the activation of ERK1/2 and Blimp-1/IRF4 upregulation. Consistently, CD4+ T cells from moderate-to-severe SLE patients with high ICAM-1 expression mediated less IgG production after T-B coculture. Therefore, ICAM-1-mediated human CD4+ T-B cell adhesion provides dual roles on B cell differentiation and IgG production partially depending on expression levels of PD-1 on B cells, supporting cell adhesion and subsequent PD-1 induction as an alternative intrinsic checkpoint for B cell differentiation.
- Published
- 2023
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