Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. I. Significant variation in repertoire expression between individual mice
Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. I. Significant variation in repertoire expression between individual mice
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BALB/c 小鼠对流感病毒血凝素免疫反应中抗体多样性的产生。
DOI：
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发表时间：
1983
影响因子：
15.3
通讯作者：
W. Gerhard
中科院分区：
文献类型：
--
作者：
L. Staudt;W. Gerhard
用来自14只BALB/c小鼠的125株抗HA杂交瘤抗体研究了BALB/c小鼠对流感病毒A/PR/8/34的血凝素(HA)抗体反应的异型性和独特型多样性。通过对51种相关流感病毒进行精细的特异性分析，评估了副典型的多样性是广泛的：观察到104个不同的副抗原。在三个例子中，从两只单独的小鼠身上分离出了无法区分的副反应性抗体。根据这些数据计算出的成人BALB/c抗HA副典型谱系的最小估计大小为1,500。通过筛选抗HA杂交瘤小组中存在的独特型(ID)来研究这种多样化谱系的产生，独特型(ID)是来自相关生殖系V基因的可变(V)区序列的标记。在来自7只BALB/c小鼠的16、1和10株抗HA杂交瘤抗体上，分别发现了V(K)21C、V(K)21B和V(K)21A、D、E或F L链亚群的3个交叉反应ID(IDx)。因此，V(K)21IDX(+)杂交瘤占抗HA杂交瘤的22%。在正常BALB/c血清中，8.6%的含K免疫球蛋白上也存在V(K)21IDX。这表明V(K)21群在BALB/c抗HA免疫应答中优先使用。用来自两只成年BALB/c小鼠的大量抗HA杂交瘤进一步研究了抗HA谱系的产生。制备兔抗鼠杂交瘤的抗独特型抗血清。一种抗ID血清定义了来自小鼠36的四个独特型和准典型相关但不完全相同的抗体家族，这些抗体占从该小鼠分离的杂交瘤抗体的31%。来自其他13只小鼠的112个抗HA杂交瘤抗体中没有一个表现出独特型交叉反应。此外，在75只BALB/c小鼠的抗PR8抗血清中未检测到该ID。另一种抗ID血清定义了来自小鼠37的27个独特型相关抗体家族，这些抗体占从该小鼠分离的杂交瘤抗体的50%。从其他13个个体分离的71个杂交瘤抗体中，只有1个是独特型交叉反应。这些结果表明，成年BALB/c小鼠表达针对流感病毒PR8血凝素的准典型和独特型不同的抗体库。基于这些观察，我们认为体细胞突变在成人抗HA谱系的产生中起着重要作用。文中还讨论了解释不同小鼠基因表达谱差异的机制。
The paratypic and idiotypic diversity of the BALB/c antibody response to the hemagglutinin (HA) of the influenza A/PR/8/34 virus (PR8) was investigated using a panel of 125 anti-HA hybridoma antibodies derived from 14 BALB/c mice. The paratypic diversity, as assessed by a fine specificity analysis using 51 related influenza viruses, was extensive: 104 distinct paratopes were observed. In three instances, antibodies with indistinguishable paratopes were isolated from two individual mice. A minimum estimate of the size of the adult BALB/c anti-HA paratypic repertoire, calculated from these data, is 1,500. The generation of this diverse repertoire was studied by screening the anti-HA hybridoma panel for the presence of idiotypes (Id) that are markers for variable (V) region sequences derived from related germ line V genes. Three cross-reactive Id (IdX) that are markers for the V(k)21C, V(k)21B, and V(k)21A, D, E, or F L chain subgroups were found, respectively on 16, 1, and 10 anti-HA hybridoma antibodies derived from seven individual BALB/c mice. Thus, the V(k)21 IdX(+) hybridomas constitute 22 percent of the anti-HA hybridoma panel. The V(k)21 IdX are also present on 8.6 percent of K-bearing immunoglobulin in normal BALB/c serum. This suggests that the V(k)21 group is used preferentially in the BALB/c anti-HA immune response. The generation of the anti-HA repertoire was further studied using large panels of anti-HA hybridomas derived from two individual adult BALB/c mice. Anti-idiotypic antisera were raised in rabbits against individual hybridomas from each mouse. One anti-Id serum defined a family of four idiotypically and paratypically related, but not identical, antibodies from mouse 36, which represented 31 percent of the hybridoma antibodies isolated from this mouse. None of the 112 anti-HA hybridoma antibodies derived from 13 other individual mice showed idiotypic cross-reactivity. Furthermore, this Id could not be detected in anti-PR8 antisera from 75 individual BALB/c mice. Another anti-Id serum defined a family of 27 idiotypically related antibodies from mouse 37, which represented 50 percent of the hybridoma antibodies isolated from this mouse. Only 1 of the 71 hybridoma antibodies isolated from 13 other individuals was idiotypically cross-reactive. These results demonstrate that individual adult BALB/c mice express paratypically and idiotypically distinct antibody repertoires to the HA of influenza virus PR8. Based on these observations, we suggest that somatic mutation plays an important role in the generation of the adult anti-HA repertoire. Mechanisms that could account for differences in repertoire expression among individual mice are discussed.
在无血清培养基中生产单克隆抗体。
影响因子：
2.2
作者：
Chang,TH;Steplewski,Z;Koprowski,H
通讯作者：
Koprowski,H
通过单克隆抗体对病毒进行抗原表征。
影响因子：
10.5
作者：
Yewdell,JW;Gerhard,W
通讯作者：
Gerhard,W