IGM-KAPPA/LAMBDA EBV HUMAN B-CELL CLONE - AN EARLY STEP OF DIFFERENTIATION OF FETAL B-CELLS OR A DISTINCT B-LINEAGE

IGM-KAPPA/LAMBDA EBV HUMAN B-CELL CLONE - AN EARLY STEP OF DIFFERENTIATION OF FETAL B-CELLS OR A DISTINCT B-LINEAGE
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DOI:
10.1016/0161-5890(92)90173-u
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发表时间:
1992-11-01
影响因子:
3.6
通讯作者:
TONNELLE, C
TONNELLE, C
中科院分区:
医学3区
文献类型:
--
作者:
CUISINIER, AM;FUMOUX, F;TONNELLE, C

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与克隆理论一致,由于等位基因和同种型排斥,一个 B 淋巴细胞合成一种抗体。我们分析了 EBV B 细胞克隆 E29.1,它源自 11 周大的胚胎,并分泌 IgMkappa 和 IgMlambda。对产生的 IgM 的结构分析表明,含 lambda 的五聚体可以被认为是杂合分子,同时表达 kappa 和 lambda 链,kappa/lambda 比率在 5 到 10 之间。还发现 60% 的 lambda 链以游离形式分泌,可能是由于 mu 链对 kappa 链有更好的亲和力。三个转录物的序列具有完整的 ORF(开放阅读框),并且非常接近然而,在 V(kappa) 和 J(kappa) 基因之间有一个额外的密码子,该密码子从未在成人骨髓瘤蛋白或 cDNA 人类序列中描述过。这一观察结果表明 kappa 链中存在 N 多样性。在 23 个 lambda 克隆的集合上分析了 Kde(kappa 删除元件)重组对 kappa/lambda 基因座激活的可能作用。 kappa 基因重排状态表明,35% 的克隆至少保留了 1 个 kappa 等位基因,而没有发生 Kde 重组,4 个 lambda 克隆在种系构型中具有 1 个 kappa 等位基因。讨论了轻链基因激活从前 B 细胞成熟到 B 细胞的不同假设。
In agreement with the clonal theory, one B lymphocyte synthetizes one antibody due to allelic and isotypic exclusion. We analyzed an EBV B-cell clone, E29.1, derived from an 11 week-old embryo, and secreting both IgMkappa and IgMlambda. Structural analysis of produced IgM, indicated that lambda-containing pentamers could be considered hybrid molecules, expressing both the kappa and the lambda chains, with a kappa/lambda ratio between 5 and 10. It was also found that 60% of the lambda chains were secreted in free form, presumably as a result of a better affinity of mu chains for kappa chains.The sequence of the three transcripts had an entirely ORF (Open Reading Frame), and were very close to germline sequences, with, however, an additional codon between V(kappa) and J(kappa) gene which has never been described in adult myeloma protein or cDNA human sequence. This observation is suggestive of N diversity taking place in kappa chains.The possible role of Kde (kappa deleting element) recombination onto kappa/lambda locus activation was analyzed on a collection of 23 lambda clones. The status of rearrangement of kappa genes indicated that 35% of these clones had retained, at least, one kappa allele without the Kde recombination, four lambda clones had one kappa allele in germline configuration. Different hypotheses of maturation from pre-B cell to B cell with activation of light chain genes are discussed.