Non‐Antigen‐Specific B Cells Induced Regulatory CD4+ T Cells Through Decreasing T Cell Activation

ABSTRACT Our previous findings demonstrated that naïve B cells elicit suppressive CD4 + regulatory T (Treg) cells, named as Treg‐of‐B cells. However, the capability of antigen‐specific B cells in that process remains unclear. Using ovalbumin (OVA) as a model antigen, the present study showed that B cells from OVA‐immunised mice decreased that ability. Instead, OVA‐activated OVA‐specific (OB1) B cells induced effector‐like T‐of‐OB1 cells without regulatory function. Phenotypically, Treg‐of‐B cells reduced the production of interferon (IFN)‐γ, interleukin (IL)‐17 and IL‐2 and expressed CD62L, PD1 and endothelial cell adhesion molecule 1 (PECAM1). Functionally, adoptive transfer of Treg‐of‐B cells significantly attenuated Th1 cell‐mediated delayed‐type hypersensitivity (DTH) responses and inhibited IFN‐γ‐producing Th1 cells, while T‐of‐OB1 cells did not. Mechanistically, activated antigen‐specific B cells increased the expression of costimulatory molecules and promoted higher T cell activation, contributing to effector T cell phenotype. Conversely, Treg‐of‐B cells exhibited lower T cell activation, possibly mediated through the expression of PECAM1, Dusp2, Dusp5, Ptpn7, Ptpn22 and Ms4a4b . These findings suggest that non‐antigen‐specific B cells elicit CD4 + Treg cells, potentially via attenuating T cell activation, whereas that capacity is absent in antigen‐specific B cells. This distinction underscores the critical role of B cell antigen specificity in immune regulation and inflammation.