Autoreactive CD19+CD20- Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2016-02, Vol.196 (4), p.1541-1549
Main Authors: Chen, Ding, Ireland, Sara J, Davis, Laurie S, Kong, Xiangmei, Stowe, Ann M, Wang, Yue, White, Wendy I, Herbst, Ronald, Monson, Nancy L
Format: Article
Language:English
Subjects:
Adult
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Antigens, CD19 - immunology
Antigens, CD20 - immunology
Autoantibodies - analysis
B-Lymphocytes - immunology
Cerebrospinal Fluid - chemistry
Cerebrospinal Fluid - cytology
Cerebrospinal Fluid - immunology
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - physiopathology
Encephalomyelitis, Autoimmune, Experimental - therapy
Female
Humans
Male
Mice
Middle Aged
Multiple Sclerosis - immunology
Myelin-Oligodendrocyte Glycoprotein - immunology
Plasma Cells - immunology
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Summary:The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and long-lived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19(+)CD20(-) plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19(+)CD20(-) plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19(+)CD20(-) B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1501376