title: B-cell regulation and its application to transplantation.
abstract: There has been increasing interest in the role played by B cells and their associated antibody in the immune response to an allograft, driven by the need to undertake antibody-incompatible transplantation and evidence suggesting that B cells play a role in acute T-cell-mediated rejection and in acute and chronic antibody-mediated rejection. This review focuses on the molecular events, both activating and inhibitory, which control B-cell activation, and considers how this information might inform therapeutic strategies. Potential targets include the BAFF (B-cell-activating factor belonging to the tumour necrosis factor family) and CD40-CD40L pathways and inhibitory molecules, such as CD22 and FcγRIIB. B cells can also play an immunomodulatory role via interleukin (IL)10 production and may contribute to transplant tolerance. The expansion of allograft-specific IL10-producing B cells may be an additional therapeutic goal. Thus, the treatment paradigm required in transplantation has shifted from that of simple B-cell depletion, to that of a more subtle, differential manipulation of different B-cell subsets.
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Menna R
authors.initials: MR
authors.lastname: Clatworthy
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D053264:B-Cell Activating Factor / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D019013:CD40 Antigens / Q000737:chemistry; D002470:Cell Survival; D017690:Cell Transplantation; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry; D007375:Interleukin-1 / Q000737:chemistry; D016753:Interleukin-10 / Q000737:chemistry; D007518:Isoantibodies / Q000737:chemistry*; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000737:chemistry; D000069283:Rituximab; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous / Q000379:methods*
chemical_list: D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; C497867:CD22 protein, human; D019013:CD40 Antigens; C499173:FCGR2B protein, human; C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007518:Isoantibodies; D017452:Receptors, IgG; D051918:Sialic Acid Binding Ig-like Lectin 2; C505719:TNFSF13B protein, human; D016753:Interleukin-10; D000069283:Rituximab
keywords: B cells; BAFF; alloantibody; antibody-mediated rejection; regulatory B cells; rituximab