ACR Convergence 2020—Because B cells play many roles in autoimmune diseases, rheumatologists have long explored B cell depletion as a reasonable strategy for the treatment of autoimmune diseases. The problem with the currently available strategies for B cell depletion, however, is that they are only partially effective, perhaps because they leave behind persistent autoimmune long-lived plasma cells.
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Explore This IssueFebruary 2021
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In healthy individuals, when inflammation resolves, these plasma cells regress, diminish in number and survive in niches in previously inflamed tissue where they are immobile. Some rheumatologists wonder if these cells may be one potential source of pathogenic autoantibodies that can contribute to humoral immunity in refractory autoimmune diseases.1
On Sunday afternoon at last fall’s conference, experts convened to discuss the future of B cell depletion given the controversy about whether pathogenic autoantibodies are produced by these cells or, alternatively, by plasmablasts and short-lived plasma cells.
B Cell Biology
Richard John Looney, MD, a professor of medicine at University of Rochester in New York, set the stage by reviewing B cell biology and identifying the problems with current B cell depleting therapies that have difficulties reaching these long-lived plasma cells.
Rheumatologists often think of B cells, explained Dr. Looney, as production factories for antibodies. But B cells have many other functions, including antigen presentation to T cells, secretion of cytokines and organization of tissue inflammation.
Antibodies, including autoantibodies in lupus, can be made by short-lived or long-lived plasma cells. Currently approved B cell depletion therapies all target CD20, a marker on naive and memory B cells, that is not on long-lived plasma cells. Not surprisingly, these therapies affect B cell functions such as antigen presentation, cytokine production and organization of tissue inflammation, and they have the potential to eliminate autoantibodies made by short-lived plasma cells that are continually derived from B cells. Unfortunately, they do not affect long-lived plasma cells.
Consequences of Depletion
Marko Radic, PhD, an associate professor of microbiology, immunology and biochemistry, University of Tennessee Health Science Center, Memphis, then spoke about the consequences of this incomplete depletion of memory B cells and short-lived plasma cells. He also described CD19-specific chimeric antigen receptor (CAR) based T cell therapy, an antibody-based immunotherapy primarily used for the treatment of B cell lineage malignancies, and its remarkable ability to deplete all CD19+ cells, including naive and memory B cells as well as short-lived plasma cells.