B Cells and B Cell Depletion in Autoimmunity and Atherosclerosis

Although previously B cells had been underestimated in comparison to T cells in their role in autoimmunity, now, their impact is well established. Via secretion of autoantibodies, presentation of autoantigens, regulation of antigen processing and presentation, and release of inflammatory cytokines, B cells can mediate cytotoxicity and lead to organ damage. B cell depletion via CD20 targeting effectively eliminates B cells in the blood and primary lymph organs and has found an effective role in the treatment of both rheumatological and neurological diseases. The neonatal Fc receptor (FcRn) is a key component of immune regulation that prevents IgG (produced by B cells) from degradation by lysosomes, sending it back into the extracellular compartment, thereby extending its half-life. This abundance of pathogenic IgG can lead to the development of autoimmune disease. The interplay between these two mechanisms of autoimmunity provides the great potential for combination therapy to reduce existent pathogenic IgG as well as prevent the production of new autoantibodies, though further investigation is needed to determine the risks, particularly of infection. This paper will explore existing B cell depleting treatments and FcRn inhibitors, and consider the potential impact for autoimmune disease as well as for the treatment of atherosclerosis.