Effector and regulatory B cells in immune-mediated kidney disease

B cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of B cell studies have focused on their pathological role as antibody producers. However, these cells have broad functions in immune responses beyond immunoglobulin secretion, including antigen presentation to T cells and cytokine production. Importantly, not all B cell subsets enhance immune responses. Regulatory B (Breg) cells attenuate inflammation and contribute to the maintenance of immune tolerance. Breg cells are numerically deficient and/or dysfunctional in several autoimmune diseases that can affect the kidneys, including systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as in some groups of renal transplant recipients with alloimmune graft damage. B cell-targeting biologics have been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect both pro-inflammatory B cells and Breg cells, potentially limiting their long-term efficacy. Future strategies might involve the modulation of pro-inflammatory B cells in combination with the stimulation of regulatory subsets. Additionally, the monitoring of individual B cell subsets in patients may lead to the discovery of novel biomarkers that could help to predict disease relapse or progression. Autoimmune diseases and kidney transplantation can result in immune-mediated kidney pathology. In this Review, the authors discuss the roles of effector and regulatory B cells and the efficacy of B cell-targeting therapies in these settings.