B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets

Abstract

Increasing recognition of the role of B cells in the adaptive immune response makes B cells an important therapeutic target in autoimmunity. Numerous current and developmental immunotherapies target B cells for elimination through recognition of cell-surface proteins expressed specifically on B cells, in particular CD19 and CD20. Similarities and differences in the function and expression of these two molecules predict some shared, and some distinct, pharmacological effects of agents targeting CD19 versus CD20, potentially leading to differences in the clinical safety and efficacy of such agents. Here, we review current knowledge of CD19 and CD20 function and biology, survey current and developmental therapies that target these molecules, and discuss potential differences in elimination of B cells by drugs that target CD19 versus CD20, with particular focus on the central nervous system autoimmune diseases multiple sclerosis and neuromyelitis optica. The principles and mechanisms herein discussed might also be relevant to a variety of other nervous system autoimmune disorders, including NMDA (N-methyl-D-aspartate) receptor encephalitis, transverse myelitis and myasthenia gravis.

Keywords: B cells; CD19; CD20; autoimmunity; experimental autoimmune encephalomyelitis; multiple sclerosis; neuromyelitis optica; neuromyelitis optica spectrum disorder; pharmacology; plasma cells; plasmablasts.

Figure 1.

Summary of CD19 and CD20 expression during B cell development. CD19 expression is observed on earlier-stage B cells than is CD20. In addition, CD19 expression is found to persist on late-stage antibody-secreting B cells (plasmablasts and plasma cells) after CD20 expression has been lost.

Figure 2.

CD19⁺CD20⁻ cells in lymphoid tissues provide immune memory. Late-stage (CD38^highCD27⁺) B cells isolated from bone marrow, spleen, tonsil and blood are predominantly CD19⁺ and almost entirely CD20⁻. In lymphoid tissues, both the CD19⁺ and CD19⁻ subsets produce antigen-specific IgG in response to prior viral exposure/vaccination. Analysis of antigen-specific IgG production by CD19⁺ cells from blood was not feasible, but the existence of such cells in primary and secondary lymphoid tissues suggests they also exist in circulation. Based on results from Groves and colleagues (Groves et al., submitted).