Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity.

Abstract

Abstract Anti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also in some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not completely understood, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgH MOGspontaneous experimental autoimmune encephalomyelitis mice in the chronic phase of disease, after the establishment of meningeal B cell clusters. Compared to the circulation, lymph nodes, and spleen, B cell depletion from the CNS was delayed and not evident until 7d post administration of anti-CD20. Further, we did not find evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. The reduction of B cell numbers in the CNS coincided with less demyelination of the spinal cord white matter and, surprisingly, an increase in the number of T cells in the meninges but not parenchyma. YT is the recipient of an endMS Doctoral Studentships from the Multiple Sclerosis Society of Canada (MSSOC). KAP is the recipient of an endMS Post-Doctoral Fellowship from MSSOC. This study was funded by operating grants from the Canadian Institutes of Health Research and the MSSOC.