Properties of regulatory B cells regulating B cell targets. Issue 12 (6th September 2021)

• Record Type: Journal Article
• Authors: Fu, Qiang; Lee, Kang Mi; Huai, Guoli; Deng, Kevin; Agarwal, Divyansh; Rickert, Charles G.; Feeney, Noel; Matheson, Rudy; Yang, Hongji; LeGuern, Christian; Deng, Shaoping; Markmann, James F.
• Is Part Of: American journal of transplantation. Volume 21:Issue 12(2021)
• Page Start: 3847
• Page End: 3857
• Publication Date: 2021-09-06
• Subjects: B cell biology -- basic (laboratory) research / science -- cellular biology -- flow cytometry -- immune regulation -- immunobiology -- immunosuppression / immune modulation -- translational research / science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16772
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Regulatory B cells (Bregs) have shown promise as anti‐rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naïve B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs‐TLR) that prevented allograft rejection. Here, we examine the granular phenotype and regulatory properties of Breg‐TLR cells suppressing B cells. Cocultures of Bregs‐TLR with LPS‐activated B cells showed a dose‐dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs‐TLR induced a decline in antibody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell‐deficient mice replenished with transgenic BCR (OB1) and TCR (OT‐II) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B cells, mediated through help from CD4 + OT‐II cells, was suppressed by OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs‐TLR suppression is associated with a block in targeted B cell differentiation controlled by PRDM1 (Blimp1). This work uncovered the regulatory properties of a new brand of Breg cells and provided mechanistic insights into potential applications of Breg therapy in transplantation. Abstract : Ex vivo generated regulatory B cells impede target B cell activities via a block in their differentiation.