AUTHOR=Tan Diaoyi , Yin Wei , Guan Fei , Zeng Wanjiang , Lee Pamela , Candotti Fabio , James Louisa K , Saraiva Camara Niels Olsen , Haeryfar S.M. Mansour , Chen Yan , Benlagha Kamel , Shi Lewis Zhichang , Lei Jiahui , Gong Quan , Liu Zheng , Liu Chaohong TITLE=B cell-T cell interplay in immune regulation: A focus on follicular regulatory T and regulatory B cell functions JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.991840 DOI=10.3389/fcell.2022.991840 ISSN=2296-634X ABSTRACT=

B cells are the core components of humoral immunity. A mature B cell can serve in multiple capacities, including antibody production, antigen presentation, and regulatory functions. Forkhead box P3 (FoxP3)-expressing regulatory T cells (Tregs) are key players in sustaining immune tolerance and keeping inflammation in check. Mounting evidence suggests complex communications between B cells and Tregs. In this review, we summarize the yin-yang regulatory relationships between B cells and Tregs mainly from the perspectives of T follicular regulatory (Tfr) cells and regulatory B cells (Bregs). We discuss the regulatory effects of Tfr cells on B cell proliferation and the germinal center response. Additionally, we review the indispensable role of B cells in ensuring homeostatic Treg survival and describe the function of Bregs in promoting Treg responses. Finally, we introduce a new subset of Tregs, termed Treg-of-B cells, which are induced by B cells, lake the expression of FoxP3 but still own immunomodulatory effects. In this article, we also enumerate a sequence of research from clinical patients and experimental models to clarify the role of Tfr cells in germinal centers and the role of convention B cells and Bregs to Tregs in the context of different diseases. This review offers an updated overview of immunoregulatory networks and unveils potential targets for therapeutic interventions against cancer, autoimmune diseases and allograft rejection.