Role of B cells in tolerance induction

Abstract

Purpose B cells are known to play a central role in humoral immunity and to boost cellular immunity, however, in a variety of experimental models, B cell subsets ameliorate inflammation and autoimmune disease, indicating that they can also play a regulatory role. Here we highlight the advances in regulatory B cell (Breg) biology of the past year with an emphasis on findings pertinent to transplantation. Several recent observations highlight the relevance to clinical transplantation. Data from at least three independent groups demonstrated that spontaneously tolerant renal transplant recipients exhibit a peripheral blood B cell signature although the significance of these data remains unclear. Moreover, new data suggest that regulatory B cells may serve as a biomarker for long-term allograft outcomes. Finally, recent evidence suggesting that plasma cells may be an essential component of Bregs raises new concerns about targeting antibody producing cells. Recent findings We describe new information on Breg mechanisms of action to suppress the alloresponse, signals to expand Bregs in vitro, and more functional evidence of Breg involvement in operationally tolerant kidney patients and in maintaining stable allograft function. Summary While lymphocyte depletion remains central to tolerance induction therapy, the sparing or expansion of regulatory B cells may be an additional strategy to preempt graft rejection.

Regulatory B Cell-Dependent Islet Transplant Tolerance Is Also Natural Killer Cell Dependent

“…A frequently described hallmark of Bregs, and the greatest common denominator of all subtypes, is the production of the immunomodulatory cytokine interleukin (IL)‐10 . However, it has become apparent that other mechanisms are at play, and IL‐10 is not always required for B cells to exert immunoregulatory functions . Nevertheless, the phenotypic diversity of Bregs appears to be greater than that of Tregs, and while Tregs are considered a distinct cell lineage, immune regulation may represent a functional state that many types of B cells can acquire in the appropriate context .…”

Aged B cells alter immune regulation of allografts in mice

“…In islet and cardiac allograft models, CD45RB and anti‐CD154 are known to act via Breg cells to enhance graft survival . Thus, an increased potency of Breg function in young recipients than in aged recipients could explain the different effects of B‐cell depletion observed between young and aged transplant recipients.…”

“…B cells also act as antigen present cells (APCs) to enhance cellular immunity toward an allograft . In addition to these proimmune functions of B cells, a subpopulation of B cells, termed regulatory B (Breg) cells, has been identified that promote immune regulation by producing IL‐10 . Hence, B‐cells play important and diverse roles that can either enhance or suppress immunity toward organ allografts.…”

Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse

“…B-lineage lymphoblasts have very low expression of T-cell costimulatory molecules and are poor antigen presenting cells. 25 In addition, recent data suggest that B cells may induce tolerance during lymphopenic states, 26 as may be seen in the posttransplant setting. To overcome this obstacle, DLI was given concurrently with the DC vaccine, which at the low dose of 1 x 10e6 CD3/kg was well tolerated, did not lead to severe GVHD and may have contributed to the immune responses seen in this setting.…”