ICAM-1 mediated cell-cell adhesion exerts dual roles on human B cell differentiation and IgG production

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 CD19^hi 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.