Meant to B: B cells as a therapeutic target in systemic lupus erythematosus

Abstract

B cells have a prominent role in the pathogenesis of systemic lupus erythematosus (SLE). They are mediators of inflammation through the production of pathogenic antibodies that augment inflammation and cause direct tissue and cell damage. Multiple therapeutic agents targeting B cells have been successfully used in mouse models of SLE; however, these preclinical studies have led to approval of only one new agent to treat patients with SLE: belimumab, a monoclonal antibody targeting B cell-activating factor (BAFF). Integrating the experience acquired from previous clinical trials with the knowledge generated by new studies about mechanisms of B cell contributions to SLE in specific groups of patients is critical to the development of new treatment strategies that will help to improve outcomes in patients with SLE. In particular, a sharper focus on B cell differentiation to plasma cells is warranted.

Figure 1. Different strategies to interfere with B cell proinflammatory function in patients with SLE.

Strategies include B cell and plasma cell depletion (e.g., antibodies directed at surface proteins or proteasome inhibitors), selective depletion of autoreactive B cells (e.g., BAFF inhibition), antigen-based therapies that block pathogenic antibodies, and prevention of B cell activation (e.g., blockade of B-T cell costimulation or B cell–activating cytokines).