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Explore This IssueJanuary 2010
B-cell depletion therapy is now routinely used in the treatment of diverse diseases, especially those refractory to conventional immunosuppressive therapy. Moreover, what once was viewed as a one-time therapy often is now used recurrently. It is critical to understand the impact of B-cell depletion on normal immune responses, the reasons B cell–targeted therapies may be efficacious in such a broad range of diseases, potential differences in B cell–directed therapies in efficacy and mechanism of action, and determination as to whether there are subsets of patients who will respond particularly well to B-cell approaches as opposed to other treatment modalities.
The Multi-layered Role of B Cells in Autoimmune Disease
To understand the efficacy of B-cell therapies, as well as treatment response heterogeneity, we need to consider the role of the B cell in autoimmune diseases. As a starting point, to borrow a phrase, autoimmune diseases are not created equal. Certain diseases may be predominantly autoantibody mediated, others may involve B cells via autoantibody-independent mechanisms such as cytokine production or antigen presentation, other disease may be T-cell driven, and many undoubtedly represent some combination of these.
The importance of antibody-independent roles for B cells is often underappreciated, but is highlighted by certain important findings: 1) In mouse lupus, B cells are critical to the development of disease even when they are unable to secrete autoantibodies1; 2) In at least some human autoimmune diseases, the efficacy of B-cell depletion is dissociated from changes in levels of autoantibodies; and 3) The most compelling efficacy data for B-cell depletion occurs in diseases that are traditionally viewed as T-cell driven (e.g., RA and MS), suggesting a role for B cells in regulating other immune cells.