Källberg E, Gray D, Leanderson T
Immunology Unit, Lund University, Sweden.
Int Immunol. 1993 Jun;5(6):573-81. doi: 10.1093/intimm/5.6.573.
We have studied somatic mutation activity early in a response to 2-phenyl-5-oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later.
我们研究了对与卵清蛋白偶联的2-苯基-5-恶唑酮（phOx-OVA）产生应答早期的体细胞突变活性。尽管已知重排至Jκ5的VκOx1基因在该应答中占主导，但其他密切相关的Vκ基因也参与其中。我们比较了在初次免疫后两个时间点，VκOx1基因以及一组重排至相同Jκ片段的相关Vκ基因中引入点突变的情况。结果表明，对单个重排底物中的突变进行定量会导致对总突变活性的低估。在应答早期，基因内存在明显的体细胞突变活性，而在应答后期可能不存在。我们还表明，在免疫后第7天，用phOx-OVA进行足垫注射后，引流淋巴结中的B细胞中已经可以检测到多个体细胞突变。数据表明存在一种系统，其中突变在应答早期作用于广泛的底物，而高亲和力互补位的选择和扩增则在后期发生。
