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

• Published in: Brain research. Molecular brain research. Vol. 34; no. 2; pp. 283 - 293
• Main Authors: Asakura, Kunihiko, Miller, David J., Pogulis, Robert J., Pease, Larry R., Rodriguez, Moses
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.12.1995; Elsevier
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal; Antigen-Antibody Reactions; Autoantibodies - immunology; Base Sequence; Biological and medical sciences; Demyelination; DNA, Complementary - genetics; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Genes, Immunoglobulin; Genetic Code; Germ Cells - physiology; Immunoglobulin Variable Region - genetics; Isolated neuron and nerve. Neuroglia; Molecular Sequence Data; Multigene Family; Multiple sclerosis; Myelin; Natural autoantibody; Oligodendroglia - immunology; Remyelination; Theiler's virus; Vertebrates: nervous system and sense organs; Theiler's virus; Multiple sclerosis; Demyelination; Myelin; Remyelination; Natural autoantibody; Immunoglobulins; Gene; Oligodendrocyte; Neuroglia; Monoclonal antibody; Aminoacid sequence
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/0169-328X(95)00190-4

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 V H was identical with unrearranged V H segment transcript A1 and A4. O4 V H had three and HNK-1 V H had six nucleotide differences from germline V H101 in the V H 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 J H and HNK-1 J H were encoded by unmutated germline J H4, whereas O1 J H was encoded by germline J H1 with one silent nucleotide change. O1 and O4 light chains were identical with myeloma MOPC21 except for one silent nucleotide change. HNK-1 V κ was identical with germline V κ41 except for two silent nucleotide changes. O1 J κ, O4 J κ and HNK J κ were encoded by unmutated germline J κ2. In contrast, A2B5 V H showed seven nucleotide differences from germline V1, whereas no germline sequence encoding A2B5 V κ 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.