Regulatory B Cells and Tolerance in Transplantation: From Animal Models to Human

Abstract

Until recently, the role of B cells in transplantation was thought to be restricted to producing antibodies that have been clearly shown to be deleterious in the long-term, but, in fact, B cells are also able to produce cytokine and to present antigen. Their role as regulatory cells in various pathological situations has also been highlighted, and their role in transplantation is beginning to emerge in animal, and also in human, models. This review summarizes the different studies in animals and humans that suggest a B-cell regulatory role in the transplant tolerance mechanisms.

Central Role of CD45RA− Foxp3hi Memory Regulatory T Cells in Clinical Kidney Transplantation Tolerance

“…51 Finally, B cells are also potential candidates for involvement in transplantation tolerance. 33 The recent description of Bregs that can induce, maintain, and expand Tregs strengthens this idea. 52 A link between Bregs and Tregs in transplantation tolerance was suggested in recent work.…”

“…31,32 Although the phenomenon of operational tolerance offers a unique model for the regulation of the immune response in humans, the mechanisms responsible for the maintenance of tolerance in these patients remain unclear. We and others previously demonstrated the possible involvement of regulatory cells, including regulatory B cells (Bregs) 33 and Tregs, 4,8,9,34 in this process. We initially reported a greater number of circulating CD4 + CD25 hi Foxp3 + cells in blood from patients with operational tolerance, 9 and previous transcriptomic studies highlighted higher mRNA levels of Foxp3 in the blood, grafts, and urine of tolerant patients compared with other transplant recipients and with HVs.…”

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

“…Edemir et al 18 used a rodent model to describe gene expression patterns that support the spontaneous simultaneous activation of immune effector–related pathways and protective and immune counter‐regulatory mechanisms as a response to the allogeneic transplant. In humans, we and others have previously described a dysregulation of B cell–related genes in tolerant recipients—associated with the maintenance or expansion of transitional B cells in peripheral blood 8, 9—that elicited new avenues toward understanding the role of transitional B cells in tolerance 19, 20, 21. Differential expression profiles associated with IS treatment have been demonstrated by Erickson et al 22 in the context of transplantation in rats.…”

Bregs in Chronic HBV: Is It Time for Bragging Rights?

“…The best understood mechanism by which Bregs suppress immune function is through secretion of IL-10, which inhibits the production of pro-inflammatory cytokines and supports regulatory T cell differentiation. The immune regulatory mechanisms of Bregs defined to date are protection from lethal inflammation, alteration of the development of autoimmune diseases, inhibition of anticancer responses in tumor models and possibly contribution to allograft tolerance [7]. Nevertheless, little is known of the contribution of Bregs to immune function in human persistent viral infections such as in chronic viral hepatitis.…”