Weiss S, Wu G E
EMBO J. 1987 Apr;6(4):927-32. doi: 10.1002/j.1460-2075.1987.tb04840.x.
Somatic point mutations are usually found in the coding and flanking regions of functionally and aberrantly rearranged immunoglobulin variable region gene segments. Mutations in the unrearranged V gene segments of myelomas or hybridomas have not been described so far. We have cloned and sequenced unrearranged V lambda gene segments from several cell lines. There were no nucleotide changes in four unrearranged V lambda segments: one V lambda 1 from a lambda 3-producing hybridoma and one V lambda 2 from a lambda 1-producing myeloma (J558) and two V lambda 2 from a kappa-producing myeloma (P3X63). However, we found somatic mutations in the unrearranged V lambda segments from the lambda 2-producing myeloma MOPC315. The unrearranged V lambda 1 gene segment had two mutations in the coding region and the unrearranged V lambda 2 had one mutation in the 3' flanking region. We also cloned and sequenced the unrearranged J lambda and C lambda gene segments of MOPC315 and found no sequence alterations. This is consistent with the notion that the overall mutation rate is not higher in this cell line. Therefore, we suggest that the somatic hypermutation system can use unrearranged V gene segments as substrates. The extensive sequencing required for this work revealed a number of errors in the reported nucleotide sequences of the Ig lambda locus in BALB/c mice.
体细胞点突变通常见于功能异常重排的免疫球蛋白可变区基因片段的编码区和侧翼区。目前尚未见骨髓瘤或杂交瘤未重排V基因片段发生突变的报道。我们从几个细胞系中克隆并测序了未重排的Vλ基因片段。4个未重排的Vλ片段未发生核苷酸改变：1个来自产生λ3的杂交瘤的Vλ1、1个来自产生λ1的骨髓瘤（J558）的Vλ2以及2个来自产生κ的骨髓瘤（P3X63）的Vλ2。然而，我们在产生λ2的骨髓瘤MOPC315的未重排Vλ片段中发现了体细胞突变。未重排的Vλ1基因片段在编码区有2个突变，未重排的Vλ2在3'侧翼区有1个突变。我们还克隆并测序了MOPC315的未重排Jλ和Cλ基因片段，未发现序列改变。这与该细胞系总体突变率不高的观点一致。因此，我们认为体细胞超突变系统可以将未重排的V基因片段用作底物。这项工作所需的广泛测序揭示了BALB/c小鼠Igλ基因座报道的核苷酸序列中的一些错误。
