TY - JOUR
T1 - Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes
AU - Asakura, Kunihiko
AU - Miller, David J.
AU - Pogulis, Robert J.
AU - Pease, Larry R.
AU - Rodriguez, Moses
N1 - Funding Information:
This study was supported by National Institute of Health (NS24180). We appreciate the generous contributions of Mr. and Mrs. E. Applebaum to this project.
PY - 1995/12/28
Y1 - 1995/12/28
N2 - 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.
AB - 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.
KW - Demyelination
KW - Multiple sclerosis
KW - Myelin
KW - Natural autoantibody
KW - Remyelination
KW - Theiler's virus
UR - http://www.scopus.com/inward/record.url?scp=0029562053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029562053&partnerID=8YFLogxK
U2 - 10.1016/0169-328X(95)00190-4
DO - 10.1016/0169-328X(95)00190-4
M3 - Article
C2 - 8750831
AN - SCOPUS:0029562053
SN - 0169-328X
VL - 34
SP - 283
EP - 293
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 2
ER -