RT Journal Article
SR Electronic
T1 Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1012
DO 10.1212/NXI.0000000000001012
VO 8
IS 4
A1 Rosa Margareta Brand
A1 Verena Friedrich
A1 Jolien Diddens
A1 Monika Pfaller
A1 Francesca Romana de Franchis
A1 Helena Radbruch
A1 Bernhard Hemmer
A1 Katja Steiger
A1 Klaus Lehmann-Horn
YR 2021
UL http://nn.neurology.org/content/8/4/e1012.abstract
AB Objective To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS).Methods We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. ɑCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry.Results ɑCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, ɑCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes.Conclusions These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that ɑCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity.ɑCD20 mAb=anti-CD20 monoclonal antibody; BCR=B-cell receptor; EAE=experimental autoimmune encephalomyelitis; mELT=meningeal ectopic lymphoid tissue; MOG=myelin oligodendrocyte glycoprotein; MPO=myeloperoxidase; MS=multiple sclerosis; RRMS=relapsing-remitting multiple sclerosis; PMS=progressive MS; SLO=secondary lymphoid organ; LFB-PAS=Luxol fast blue and periodic acid-Schiff reaction; TCR=T-cell receptor