Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: past, present, and future

Abstract

It has long been known that B cells produce autoantibodies and, thereby, contribute to the pathogenesis of many autoimmune diseases. Systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disorder, is characterized by high-circulating autoantibody titers and immune-complex deposition that can trigger inflammatory damage in multiple organs/organ systems. Although the interest in B cells in SLE has historically focused on their autoantibody production, we now appreciate that B cells have multiple autoantibody-independent roles in SLE as well. B cells can efficiently present antigen and activate T cells, they can augment T cell activation through co-stimulatory interactions, and they can produce numerous cytokines which affect inflammation, lymphogenesis, and immune regulation. Not surprisingly, B cells have become attractive therapeutic targets in SLE. With these points in mind, this review will focus on the autoantibody-dependent and autoantibody-independent roles for B cells in SLE and on therapeutic approaches that target B cells.

Figure 1

B cells produce a variety of autoantibodies in SLE. The relevant utility and clinical associations of those autoantibodies are enumerated.

Figure 2

B cells have multiple functions in SLE pathogenesis, including proinflammatory and immunoregulatory cytokine production, antigen presentation to and co-stimulation of T cells, and autoantibody production.

Figure 3

In light of the numerous functions of B cells in SLE, a number of therapeutic strategies have been developed in an attempt to target directly or indirectly B cells and their effects.