Wilson M, Hsu E, Marcuz A, Courtet M, Du Pasquier L, Steinberg C
Basel Institute for Immunology, Switzerland.
EMBO J. 1992 Dec;11(12):4337-47. doi: 10.1002/j.1460-2075.1992.tb05533.x.
Although the Xenopus immunoglobulin heavy chain locus is structurally and functionally similar to mammalian IgH loci, Xenopus antibodies are limited in heterogeneity, and they mature only slightly in affinity during immune responses. During the antibody response of isogenic frogs to DNP-KLH, mu and upsilon cDNA sequences using elements of the VH1 family were cloned, sequenced and compared with germline counterparts. There were zero to four mutations per sequence, mostly single base substitutions, in the framework and CDRs 1 and 2 of VH. No mutations were found in JH. Since the point mutation rate was only 4- to 7-fold lower than that calculated for mice, affinity maturation does not seem to be limited by mutant availability. Because of a relatively low ratio of replacement to silent mutations in the CDRs and a very high ratio of GC to AT base pairs altered by mutation, it is suggested that the problem results from the absence of an effective mechanism for selecting mutants, which in turn might be related to the absence of germinal centers in Xenopus.
尽管非洲爪蟾免疫球蛋白重链基因座在结构和功能上与哺乳动物的IgH基因座相似，但非洲爪蟾抗体的异质性有限，并且在免疫反应过程中其亲和力仅略有成熟。在同基因蛙对DNP-KLH的抗体反应过程中，利用VH1家族的元件克隆、测序了μ和υ cDNA序列，并与种系对应序列进行了比较。VH的框架区以及互补决定区（CDR）1和2中，每个序列有0至4个突变，大多为单碱基替换。在JH中未发现突变。由于点突变率仅比小鼠计算出的突变率低4至7倍，亲和力成熟似乎不受突变体可用性的限制。由于CDR中替换突变与沉默突变的比例相对较低，且突变改变的GC与AT碱基对的比例非常高，因此有人认为问题在于缺乏选择突变体的有效机制，这反过来可能与非洲爪蟾中没有生发中心有关。
