Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes

Kunihiko Asakura, David J. Miller, Robert J. Pogulis, Larry R. Pease, Moses Rodriguez

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Abstract

Natural or physiologic autoantibodies are present normally in serum, are polyreactive, are frequently of the IgM subtype, and are encoded by unmutated germline genes. We tested whether the oligodendrocyte-reactive O1, O4, A2B5, and HNK-1 IgMκ monoclonal antibodies are natural autoantibodies by sequencing immunoglobulin (Ig) cDNAs and comparing these with published germline sequences. O1 VH was identical with unrearranged VH segment transcript A1 and A4. O4 VH had three and HNK-1 VH had six nucleotide differences from germline VH101 in the VH coding region. The D segment of O1 was derived from germline SP2 gene family. The D segments of O4 and HNK-1 were derived from DFL16 gene family. O4 JH and HNK-1 JH were encoded by unmutated germline JH4, whereas O1 JH was encoded by germline JH1 with one silent nucleotide change. O1 and O4 light chains were identical with myeloma MOPC21 except for one silent nucleotide change. HNK-1 Vκ was identical with germline Vκ41 except for two silent nucleotide changes. O1 Jκ, O4 Jκ and HNK Jκ were encoded by unmutated germline Jκ2. In contrast, A2B5 VH showed seven nucleotide differences from germline V1, whereas no germline sequence encoding A2B5 Vκ was identified. O1 and O4, but not A2B5 were polyreactive against multiple antigens by direct ELISA. Therefore, O1, O4 and HNK-1 Igs are encoded by germline genes, and have the genotype and phenotype of natural autoantibodies.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalMolecular Brain Research
Volume34
Issue number2
DOIs
StatePublished - Dec 28 1995

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Keywords

  • Demyelination
  • Multiple sclerosis
  • Myelin
  • Natural autoantibody
  • Remyelination
  • Theiler's virus

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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