Targeting B Cells and Plasma Cells in Glomerular Disease

Loss of tolerance and the production of self-reactive autoantibodies by the humoral immune system are central to the pathogenesis of many glomerular diseases. These antibodies are produced by plasmablasts and plasma cells, the end products of B-cell lineage development within the bone marrow and secondary lymphoid tissues. In addition to antibody production, B cells also present antigen to T cells and produce proinflammatory cytokines. Nontargeted immunosuppression has shown efficacy in glomerular disease but is associated with multiple side effects, and there remains a high proportion of patients with resistant disease. In this article, we will review the biology of antibody-secreting cells and focus on therapeutics that specifically target B cells and plasma cells. We will review B-cell depletion strategies, including anti-CD20 monoclonal antibodies, B-cell–activating factor, and a proliferation-inducing ligand inhibition and B-cell receptor inhibition, highlighting their role in different glomerular diseases and outlining reasons for therapeutic resistance. We will also review plasma cell–directed therapies including proteasome inhibition and anti-CD38 therapies and discuss novel treatments including chimeric antigen receptor-T therapy and bispecific T-cell engagers.