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Properties of regulatory B cells regulating B cell targets

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.