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Anti-MOG antibodies are under polygenic regulation with the most significant control coming from the C-type lectin-like gene locus

Genes & Immunity volume 14, pages 409–419 (2013)Cite this article

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Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is genetically complex. There is evidence supporting a role of myelin oligodendrocyte glycoprotein (MOG) humoral immunity in MS. We aimed to determine the genetic regulation of anti-MOG antibodies and their involvement in disease, by using MOG-induced experimental autoimmune encephalomyelitis (EAE) in rat, an animal model that closely mimics human MS. We show polygenic regulation of anti-MOG antibodies in two backcross populations, including a major genetic determinant for antibody expression on chromosome 4, Amig3. We fine-mapped the region to 539 kilobases (kb) consisting of a complex of seven C-type lectin receptor genes (Dcir4, Dcir3, Dcir2, Dcir1, Dcar1, Mcl and Mincle) that was captured in the APLEC congenic strain. We confirmed that Amig3 regulates anti-MOG antibody levels in MOG-EAE, and further showed that immune reactions during initiation of EAE were skewed toward increased numbers of B cells in the EAE-protected APLEC strain, together with higher anti-MOG IgG1 and lower IgG2b levels. Taken together, our data demonstrated complex regulation of the antibody response during EAE and that skewing the antibody response toward Th2 contributed to protection from EAE.

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Acknowledgements

This work was supported by the Swedish research council, the Swedish Brain foundation, the European Community’s Seventh Framework Programme (FP7/2007–2013) under Grant agreement HEALTH-F4-2010-241504 (EURATRANS), Knut and Alice Wallenberg Foundation and the Swedish foundation for neurologically disabled (NHR).

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  1. Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden

    S Flytzani, P Stridh, A O Guerreiro-Cacais, M Marta, M T Hedreul, M Jagodic & T Olsson

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  1. S Flytzani
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Correspondence to S Flytzani.

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Flytzani, S., Stridh, P., Guerreiro-Cacais, A. et al. Anti-MOG antibodies are under polygenic regulation with the most significant control coming from the C-type lectin-like gene locus. Genes Immun 14, 409–419 (2013). https://doi.org/10.1038/gene.2013.33

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