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bioRxiv · 10.64898/2026.10.12.755729

IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network

Baert, L.·Caffiers, A.·Yang, A.·Choi, S.·Bose, S.·Oh, S.
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Abstract

B cells can control inflammation, but the factors governing B cell-mediated immune regulatory network remain unclear. We report that IL-2/CD40L enable class-switched memory (CSM) B cells to acquire an immunosuppressive phenotype characterized by the expression of surface TIGIT as well as multiple other inhibitory receptors (PD-1, LAG-3, GITR, CD39, and CTLA-4) and soluble molecules (IL-10, granzyme B, and IL-35). TIGIT+ CSM B cells expressing functional CCR9 exhibit significant defects in total immunoglobulin secretion, while preserving IgA2 secretion. Furthermore, IL-2/CD40L-induced ex vivo-generated TIGIT+ CSM B cells suppress human T cell-mediated inflammation in a xenogeneic mouse model of acute graft-versus-host disease, while promoting IL-10-producing regulatory T cell (Treg) response. These findings identify IL-2/CD40L as key drivers of a B cell-mediated immune regulatory network, especially by generating TIGIT+ CSM B cells that can further promote Treg response. This study supports the development of TIGIT+ B cell-based therapy models for inflammatory diseases.

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Baert, L., Caffiers, A., Yang, A., Choi, S., Bose, S., Oh, S.. 2026-10-18. IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network. https://doi.org/10.64898/2026.10.12.755729

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