Abstract
B cell-mediated antigen presentation is required to induce functional pathogenicity of CD4 T cells in a proteolipid protein mouse model of multiple sclerosis
The Journal of immunology (1950), Vol.208(1_Supplement), pp.103-103.08
05/01/2022
DOI: 10.4049/jimmunol.208.Supp.103.08
Abstract
Abstract Given the success of B cell depletion therapy in multiple sclerosis (MS), deeper understanding of pathogenic B cells will be key in developing novel treatments. Notably, B cell depletion therapy leaves plasma cells and immunoglobulin levels largely intact, indicating that B cells provide pathogenic functions beyond antibodies. To better understand this, we recently developed a novel B cell-dependent, antibody-independent experimental autoimmune encephalomyelitis (EAE) mouse model of MS featuring immunoreactivity to the extracellular domains of myelin proteolipid protein (PLPECD). In contrast to a B cell-independent EAE model, we demonstrate here that PLPECD induced EAE in WT but not B cell-depleted mice, and that established disease was ameliorated by B cell depletion. We tested antigen presentation by B cells through mixed bone marrow chimeras and demonstrate that mice in which MHC II deficiency is restricted to B cells alone failed to exhibit EAE compared to MHC II sufficient mice. Given that HLA class II is the largest molecular link to MS incidence and CD4 T cells are causative in EAE, we tested B cells’ influence on CD4 T cells. In the absence of B cells, we observed not only lower activation and proliferation of CD4 T cells, but also noted a lower proinflammatory functional profile amongst the activated cells. Further, adoptively transferred CD4 T cells derived from B cell-depleted donors induced significantly less EAE compared to those from B cell-sufficient donors. These results demonstrate that antigen presentation by B cells plays a critical role in the activation, proliferation, function and pathogenicity of autoreactive CD4 T cells in demyelinating disease. Supported by grants from NIAID/NIH AI156123 and US Veterans Affairs I01BX003677.
Details
- Title: Subtitle
- B cell-mediated antigen presentation is required to induce functional pathogenicity of CD4 T cells in a proteolipid protein mouse model of multiple sclerosis
- Creators
- Alexander W. BoydenConnor R. WilhelmMohit UpdahyeNitin J. Karandikar
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.208(1_Supplement), pp.103-103.08
- DOI
- 10.4049/jimmunol.208.Supp.103.08
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2022
- Academic Unit
- Pathology
- Record Identifier
- 9984355057302771
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