B lymphocytes in transplantation (abstract)

Abstract

B lymphocytes are cells of the lymphoid lineage that express antibody as their surface antigen receptor (BCR). The principle purpose of B cell activation by antigen is to induce their differentiation into antibody-producing plasma cells, via a germinal centre reaction ( Figure 1 ). In addition, B cells act as important antigen-presenting cells, activating CD4 T cells and may also produce immunoregulatory cytokines such as interleukin (IL)IL10. B cells influence allograft outcomes in transplantation via antibody production (HLA and non-HLA antibodies) contributing to acute and chronic antibody-mediated rejection (ABMR), may drive T cell mediated rejection (TCMR) via antigen presentation, and influence the development of transplant tolerance via IL10 production [1] . A better understanding of basic B cell biology is required to develop therapeutic strategies that target B cells, allowing improved control of humoral responses in transplantation; Data show that the B cell activation threshold is determined by BCR affinity for antigen and by positive and negative co-signals, including those provided by CD4 T cells, such as co-stimulation via CD40-CD40L interactions and via cytokines such as IL4 and IL21 and those produced by myeloid cells, for example, BAFF [2] . High serum levels of BAFF have been associated with an increased risk of developing de novo donor-specific antibodies and of ABMR in sensitised subjects [3] , [4] . A small proportion of plasma cells arising from the germinal centre become established as long-lived plasma cells in the bone marrow. They reside within a number of limited niches, do not proliferate, but act as long-term antibody factories, producing IgG. Plasma cells have also been described in inflamed tissues in autoimmunity and within allografts [5] . A number of these processes may be amenable to therapeutic targeting, and this will be discussed [6] .