MOLECULAR-BASIS OF AN ISOGENEIC ANTI-IDIOTYPIC RESPONSE
MOLECULAR-BASIS OF AN ISOGENEIC ANTI-IDIOTYPIC RESPONSE
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DOI：
10.1002/j.1460-2075.1984.tb02247.x
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发表时间：
1984-01-01
期刊：
影响因子：
11.4
通讯作者：
RAJEWSKY, K
中科院分区：
文献类型：
--
作者：
SABLITZKY, F;RAJEWSKY, K
测定了6株识别2株与4-羟基-3-硝基苯乙酰(NP)半抗原有特异性的同源抗独特位抗体重链和轻链可变区基因的核苷酸序列。在两个独立获得的抗独特位细胞系[小鼠杂交瘤A25.9.7和A31.90细胞]中，原来有相同或高度同源的V.kappa、VH和D区基因重排。这两个品系在D的边界表达长的和部分同源的N序列(推测不是生殖系起源)，导致CDR3的异常长度。在第三个抗独特位抗体的重链中也存在一个由N个序列部分编码的异常长的CDR3。其余3个抗独特位抗体的VH区来源于一个VH基因，该基因与其他抗独特位抗体中表达的VH基因属于同一VH组。这些抗体中有两个表达类似的V、D和J元素，是从同一只小鼠身上分离出来的，似乎是通过至少两轮体细胞突变而从相同的B细胞前体分离出来的。体细胞点突变发生在大多数(如果不是全部)反独特体V区序列中。在2个例子中，J基因的体细胞突变增加了抗独特位之间的结构同源性。因此，该系统中的抗独特型反应受到遗传限制，并可能取决于非生殖系序列的选择，这表明该系统中抗独特型抗体表达频率低的原因。
The nucleotide sequences of the variable region genes expressed in the heavy and light chains of 6 isogeneic anti-idiotope antibodies recognizing idiotopes on 2 closely related antibodies with specificity for the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) were determined. In 2 independently derived anti-idiotope cell lines [mouse hybridoma A25.9.7 and A31.90 cells] the same or strongly homologous V.kappa., VH and D region genes had originally been rearranged. The 2 lines express long and partly homologous N sequences (presumed to be not of germ line origin) at the border of D, resulting in CDR3 of unusual length. An unusually long CDR3, partly encoded by N sequences, is also present in the heavy chain of a third anti-idiotope antibody. The VH regions of the 3 remaining anti-idiotope antibodies originate from a single VH gene which belongs to the same VH group as the VH genes expressed in the other anti-idiotopes. Two of these antibodies, expressing similar V, D and J elements, had been isolated from the same mouse and appear to have diverged from the same B cell precursor by at least 2 rounds of somatic mutation. Somatic point mutations have occurred in most, if not all anti-idiotope V region sequences. In 2 instances somatic mutations in J increase the structural homology between anti-idiotopes. The anti-idiotypic response in this system is thus genetically restricted and may depend upon the selection of non-germ line sequences, suggesting an explanation for the low frequency at which anti-idiotope antibodies are expressed in this system.