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Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response.
J Immunol. 1999 Jul 01; 163(1):40-9.JI

Abstract

Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 n) rats with Lewis (LEW) (RT1 l) and two reciprocal MHC congenic strains, LEW.1N (RT1n) and BN.1L (RT1 l). This comparison revealed that disease severity and clinical course were strongly influenced by the MHC haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.

Authors+Show Affiliations

Department of Neuroimmunology, Max-Planck Institute for Neurobiology, Martinsried, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10384097

Citation

Stefferl, A, et al. "Myelin Oligodendrocyte Glycoprotein Induces Experimental Autoimmune Encephalomyelitis in the "resistant" Brown Norway Rat: Disease Susceptibility Is Determined By MHC and MHC-linked Effects On the B Cell Response." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 1, 1999, pp. 40-9.
Stefferl A, Brehm U, Storch M, et al. Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. J Immunol. 1999;163(1):40-9.
Stefferl, A., Brehm, U., Storch, M., Lambracht-Washington, D., Bourquin, C., Wonigeit, K., Lassmann, H., & Linington, C. (1999). Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. Journal of Immunology (Baltimore, Md. : 1950), 163(1), 40-9.
Stefferl A, et al. Myelin Oligodendrocyte Glycoprotein Induces Experimental Autoimmune Encephalomyelitis in the "resistant" Brown Norway Rat: Disease Susceptibility Is Determined By MHC and MHC-linked Effects On the B Cell Response. J Immunol. 1999 Jul 1;163(1):40-9. PubMed PMID: 10384097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. AU - Stefferl,A, AU - Brehm,U, AU - Storch,M, AU - Lambracht-Washington,D, AU - Bourquin,C, AU - Wonigeit,K, AU - Lassmann,H, AU - Linington,C, PY - 1999/6/29/pubmed PY - 1999/6/29/medline PY - 1999/6/29/entrez SP - 40 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 1 N2 - Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 n) rats with Lewis (LEW) (RT1 l) and two reciprocal MHC congenic strains, LEW.1N (RT1n) and BN.1L (RT1 l). This comparison revealed that disease severity and clinical course were strongly influenced by the MHC haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10384097/Myelin_oligodendrocyte_glycoprotein_induces_experimental_autoimmune_encephalomyelitis_in_the_"resistant"_Brown_Norway_rat:_disease_susceptibility_is_determined_by_MHC_and_MHC_linked_effects_on_the_B_cell_response_ DB - PRIME DP - Unbound Medicine ER -