Immunoregulatory role of B lymphocytes in alloresponse to kidney transplant.

B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection. This function is provided by the regulatory B cells, which negatively control the immune response by producing suppressor cytokines (IL-10, IL-35, TGF-β), natural antibodies and through cellular interactions. In effect they inhibit the development of Th1 and Th17 effector cells, and induce differentiation of regulatory T cells. Operational immune tolerance in human kidney transplant recipients was associated with increased number of naïve and transitional B cells of regulatory function, and increased gene expression for differentiation of B cells. However, in chronic alloantibody transplant rejection the distorted distribution and function of regulatory B cells was found, which implies their pivotal role in graft tolerance. Currently, the immunosuppressive regimens unselectively inhibit the activity of T and B cells, by interfering with their effector and immunoregulatory functions. They do not fully control the chronic rejection reaction, which is the major cause of graft loss. Comprehension of the mechanisms of immunologic homeostasis dependent on B cells can help develop immunosuppressive protocols targeted at tolerance.