Regulation of neuroinflammation by B cells and plasma cells

The remarkable success of anti-CD20 B cell depletion therapies in reducing the burden of multiple sclerosis (MS) disease has prompted significant interest in how B cells contribute to neuroinflammation. Most focus has been on identifying pathogenic CD20(+) B cells. However, an increasing number of studies have also identified regulatory functions of B lineage cells, particularly the production of IL-10, as being associated with disease remission in anti-CD20-treated MS patients. Moreover, IL-10-producing B cells have been linked to the attenuation of inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. In addition to IL-10-producing B cells, antibody-producing plasma cells (PCs) have also been implicated in suppressing neuroinflammation. This review will examine regulatory roles for B cells and PCs in MS and EAE. In addition, we speculate on the involvement of regulatory PCs and the cytokine BAFF in the context of anti-CD20 treatment. Lastly, we explore how the microbiota could influence anti-inflammatory B cell behavior. A better understanding of the contributions of different B cell subsets to the regulation of neuroinflammation, and factors that impact the development, maintenance, and migration of such subsets, will be important for rationalizing next-generation B cell-directed therapies for the treatment of MS.

Automated summary

Studies have shown that in anti-CD20-treated multiple sclerosis (MS) patients, B cells and plasma cells not only have pathogenic roles, but also regulatory functions, such as producing IL-10. These cells' regulatory functions are associated with the alleviation of neuroinflammation, and understanding them is crucial for rationalizing next-generation B cell-directed therapies for MS.