1. B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on immunization with protein rather than short peptide, while B cell invasion of the CNS in autoimmunity does not.
- Author
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Dang AK, Jain RW, Craig HC, and Kerfoot SM
- Subjects
- Animals, Antigens, CD metabolism, Disease Models, Animal, Dose-Response Relationship, Immunologic, Encephalomyelitis, Autoimmune, Experimental chemically induced, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation genetics, Myelin Sheath metabolism, Myelin Sheath pathology, Myelin-Associated Glycoprotein toxicity, Peptides chemistry, Peptides immunology, Receptors, Antigen, T-Cell genetics, T-Lymphocytes immunology, Time Factors, Autoantigens immunology, Autoimmunity immunology, B-Lymphocytes immunology, Central Nervous System immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Myelin-Associated Glycoprotein immunology
- Abstract
We develop a new fusion protein reagent (MOGtag), based on the extracellular domain of mouse myelin oligodendrocyte glycoprotein (MOG1-125), designed to induce autoimmune responses in mice that incorporates both T and B cell recognition of antigen. Reports of similar reagents, primarily based on foreign MOG proteins, rely largely on disease incidence and severity, with little analysis of the underlying immune response or pathology. We characterize the immune response and central nervous system autoimmune disease elicited by MOGtag in mice and find that it results in the formation of a T cell-dependent germinal center B cell response. Unlike immunization with the short MOG35-55 peptide, this response incorporated B cells able to recognize MOG protein. The autoimmune disease resulting from immunization with MOGtag was chronic with clear evidence of an ongoing immune response and active white and gray matter infiltration by T cells as well as formation of B cell clusters in the meninges. Interestingly, development of B cell clusters was not absolutely dependent on the ability of B cells to recognize MOG protein, as they were also present in mice immunized with short peptide and in mice with a mutant B cell receptor specific for an irrelevant antigen., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2015
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