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Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis

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Abstract

Autoantibody responses against conformational epitopes of myelin/oligodendrocyte glycoprotein (MOG) possess myelin destructive potential, as demonstrated in the marmoset model of human multiple sclerosis (MS) and in some rodent models of experimental allergic encephalomyelitis. We have previously characterized monoclonal Fab fragments specific for conformational epitopes of MOG that were derived from a combinatorial antibody library generated from a MOG-immune marmoset. In this paper, we address the molecular heterogeneity of humoral responses against MOG in this outbred model of MS by studying additional antibody clones derived from a genetically unrelated animal. We find that all MOG-specific IgGκ Fab fragments, unrelated to genetic make-up, utilize a restricted set of variable region genes, IGHV1 and IGHV3 for the H chain and IGKV1, IGKV3, and IGKV5 for the L chain. Despite these restricting factors, diversity within these antibody repertoires can be observed, predominantly within the H-chain CDR3 regions. Our findings suggest that only a limited set of Ig genes is necessary to launch a diverse, destructive humoral immune response against a single CNS antigen in primates. These results are the first to contribute to a better understanding of how myelin-directed and potentially destructive autoantibody responses may develop in human MS.

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Notes

  1. The nomenclature of Ig genes is derived from the HUGO Gene Nomenclature Committee http://www.gene.ucl.ac.uk/nomenclature).

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Acknowledgements

The authors thank Ishita Barman, Cameron B. Nabavi, Antje Fuhrmann, and Salomon Martinez for technical assistance. This work was supported by grants from the National Multiple Sclerosis Society (RG3370-A-3 and 3438-A-7 to CPG), the National Institutes of Health (RO1.AI43073 and RO1.NS46678-01), and the Cure MS Now and Lunardi Foundations. HCvB was a postdoctoral research fellow supported by the Hertie-Stiftung, the Deutsche MS Gesellschaft, the National Institutes of Health, and the National Multiple Sclerosis Society. TM was a postdoctoral research fellow of the National Multiple Sclerosis Society.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Zürich, 8091, Zürich, Switzerland

    H.-Christian von Büdingen

  2. Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, San Francisco, CA, 94143-0114, USA

    H.-Christian von Büdingen, Til Menge, Stephen L. Hauser & Claude P. Genain

  3. Department of Neurology, University Hospital Düsseldorf, 40225, Düsseldorf, Germany

    Til Menge

Authors
  1. H.-Christian von Büdingen
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  2. Til Menge
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  3. Stephen L. Hauser
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  4. Claude P. Genain
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Corresponding author

Correspondence to Claude P. Genain.

Additional information

Sequences reported in this paper are available at Genbank under accession numbers AF393229 to AF393240 and DQ005534 to DQ005541.

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von Büdingen, HC., Menge, T., Hauser, S.L. et al. Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis. Immunogenetics 58, 122–128 (2006). https://doi.org/10.1007/s00251-006-0100-y

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  • DOI: https://doi.org/10.1007/s00251-006-0100-y

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