Age-associated B cells in autoimmune diseases

Abstract

Age-associated B cells (ABCs) are a transcriptionally and functionally unique B cell population. In addition to arising with age and following infection, ABCs are expanded during autoimmune disease, including those with systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. The exact nature of how ABCs impact disease remains unclear. Here, we review what is known regarding ABC development and distribution during diseases including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. We discuss possible mechanisms by which ABCs could contribute to disease, including the production of cytokines and autoantibodies or stimulation of T cells. Finally, we speculate on how ABCs might act as mediators between sex, infection, and autoimmune disease, and discuss avenues for further research.

Keywords: Age-associated B cell; Atypical B cell; Multiple sclerosis; Systemic lupus erythematosus; T-bet B cell.

Fig. 1

Age-associated B cells in health versus autoimmune disease Age-associated B cells (ABCs) differentiate from a combination of signals that include BCR stimulation and TLR7/9 engagement, in addition to CD40, IFNγ, and IL-21 signals, likely provided by T follicular helper cells. During times of health, ABCs are maintained at low levels in the spleen, bone marrow, and circulation, and are nearly undetectable in tonsil and lymph nodes. During autoimmune disease, ABC quantity is increased, and ABCs circulate and are present at the site of disease. ABCs produce anti-viral antibodies and cytokines in healthy individuals during viral infection. During autoimmune disease, ABCs produce both protective and inflammatory cytokines, stimulate T cells, and produce autoantibodies.