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

The study reveals that IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network. The researchers discovered that these two factors enable class-switched memory (CSM) B cells to adopt an immunosuppressive phenotype. This phenotype is marked by the expression of surface TIGIT, along with other inhibitory receptors like PD-1, LAG-3, GITR, CD39, and CTLA-4. Additionally, the CSM B cells produce soluble molecules such as IL-10, granzyme B, and IL-35.

TIGIT+ CSM B cells with functional CCR9 display significant impairments in total immunoglobulin secretion, yet they continue to secrete IgA2. Moreover, the ex vivo-generated TIGIT+ CSM B cells can suppress human T cell-mediated inflammation in a xenogeneic mouse model of acute graft-versus-host disease. Surprisingly, these B cells also promote an IL-10-producing regulatory T cell (Treg) response.

The findings demonstrate that IL-2/CD40L are key drivers of a B cell-mediated immune regulatory network. Notably, these factors generate TIGIT+ CSM B cells, which further enhance the Treg response. This research supports the development of TIGIT+ B cell-based therapy models for treating inflammatory diseases.