Oligodendrocyte-reactive 01, 04, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes
Oligodendrocyte-reactive 01, 04, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes
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DOI：
10.1016/0169-328x(95)00190-4
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发表时间：
1995-12-28
期刊：
影响因子：
--
通讯作者：
Rodriguez, M
中科院分区：
文献类型：
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作者：
Asakura, K;Miller, DJ;Rodriguez, M
天然或生理性自身抗体通常存在于血清中，是多反应性的，通常是IgM亚型，并且由未突变的生殖系基因编码。我们通过对免疫球蛋白（IG）cDNA进行测序并将其与已发表的种系序列进行比较，检测了少突胶质细胞反应性01、04、A2 B5和HNK-1 IgM κ单克隆抗体是否为天然自身抗体。01 V-H与未重排的V-H片段转录本A1和A4相同。在V-H编码区，HNK-1 V-H与V（H）101有6个核苷酸差异，HNK-04 V-H与V（H）101有3个核苷酸差异。01的D片段来源于生殖系SP2基因家族。04和HNK-1的D片段来自DFL 16基因家族。04 J（H）和HNK-1 J（H）由未突变的种系J（H）4编码，而01 J（H）由种系J（H）1编码，具有一个沉默核苷酸变化。01和04轻链与骨髓瘤MOPC 21相同，除了一个沉默的核苷酸变化。HNK-1V-κ与种系V（κ）41相同，除了两个沉默的核苷酸变化。01 J（kappa）、04 J（kappa）和HNK J（kappa）由未突变的生殖系J（kappa）2编码。相比之下，A2 B5 V-H显示出与种系V1的7个核苷酸差异，而未鉴定出编码A2 B5 V-kappa的种系序列。01和04，而不是A2 B5对多种抗原的多反应性通过直接ELISA。因此，01、04和HNK-1 Ig是由生殖系基因编码的，具有天然自身抗体的基因型和表型。
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 01, 04, A2B5, and HNK-1 IgM kappa monoclonal antibodies are natural autoantibodies by sequencing immunoglobulin (Ig) cDNAs and comparing these with published germline sequences. 01 V-H was identical with unrearranged V-H Segment transcript A1 and A4. 04 V-H had three and HNK-1 V-H had six nucleotide differences from germline V(H)101 in the V-H coding region. The D segment of 01 was derived from germline SP2 gene family. The D segments of 04 and HNK-1 were derived from DFL16 gene family. 04 J(H) and HNK-1 J(H) were encoded by unmutated germline J(H)4, whereas 01 J(H) was encoded by germline J(H)1 with one silent nucleotide change. 01 and 04 light chains were identical with myeloma MOPC21 except for one silent nucleotide change. HNK-1 V-kappa was identical with germline V(kappa)41 except for two silent nucleotide changes. 01 J(kappa), 04 J(kappa) and HNK J(kappa) were encoded by unmutated germline J(kappa)2. In contrast, A2B5 V-H showed seven nucleotide differences from germline V1, whereas no germline sequence encoding A2B5 V-kappa was identified. 01 and 04, but not A2B5 were polyreactive against multiple antigens by direct ELISA. Therefore, 01, 04 and HNK-1 Igs are encoded by germline genes, and have the genotype and phenotype of natural autoantibodies.