2025年江伯倫老師實驗室論文發表--免疫所博士班簡芊卉、碩士班葉采穎

Non-antigen-specific B cells induced regulatory CD4⁺ T cells through decreasing T cell activation

Chien-Hui Chien¹, Tsai-Ying Yeh², Bor-Luen Chiang^{2, 3*}

1. Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu County, Taiwan.
2. Genome and Systems Biology Degress Program, College of Life Science, National Taiwan University, Taipei City, Taiwan.
3. Department of Pediatrics, National Taiwan University Hospital, Taipei City, Taiwan.

AbstractOur previous findings demonstrated that naive 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 model antigen, the present study showed that naïve wild-type B cells induced suppressive Treg-of-B cells, whereas B cells from OVA-immunized 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 productions 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 in vivo and inhibited IFN-γ-producing Th1 cells in vitro, while T-of-OB1 cells did not. Mechanistically, antigen-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+ T cells, potentially via attenuating T cell activation, whereas that capacity absent in antigen-specific B cells. This distinction underscores the critical role of B cell antigen specificity in immune regulation and inflammation.

Keywords: Regulatory T (Treg) cells, suppressive function, interferon (IFN)-γ, costimulatory molecules, T cell activation, antigen-specificity

Immunology. 2025 May 4

https://onlinelibrary.wiley.com/doi/10.1111/imm.13940