Genetic control of the humoral immune response to xenografts .2. Monoclonal antibodies that cause rejection of heart xenografts are encoded by germline immunoglobulin genes.
Genetic control of the humoral immune response to xenografts .2. Monoclonal antibodies that cause rejection of heart xenografts are encoded by germline immunoglobulin genes.
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DOI：
10.1097/00007890-199560120-00023
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发表时间：
1995-12-27
期刊：
影响因子：
6.2
通讯作者：
Makowka, L
中科院分区：
文献类型：
--
作者：
Borie, DC;Cramer, DV;Makowka, L
在密切相关物种之间交换的异种移植物的排斥反应的早期阶段由强烈的体液免疫应答主导。我们最近使用接头介导的聚合酶链反应（LM-PCR）来生成IG重链和轻链特异性cDNA文库，以检查原型IgM单克隆抗体HAR-1的IG基因控制，该抗体导致仓鼠异种移植物的超急性排斥反应。结果表明，HAR-1杂交瘤细胞系由IG V-H和J（H）基因编码，HAR-1 V-H基因cDNA序列与新生儿LEW肝分离的该基因的生殖系等价物的比较（暂时命名为V（H）HAR-1）的序列分析表明，两个V-H序列共有99.3%的核酸同一性。类似地，HAR-1单克隆使用与GeneBank中可获得的J（H）1核酸序列具有98.2%同一性的IG J（H）基因。在生殖系构型中使用IG V-H和J（H）基因类似于对感染因子和自身抗体的多反应性天然抗体。这些体液应答被认为是刺激不依赖T细胞的B细胞亚群（B-1 a/B-1 B亚群）的结果，该亚群负责产生抗体，该抗体用作对抗感染性疾病的原始体液（天然抗体）防御机制。我们的研究结果表明，在仓鼠-大鼠模型中异种移植物排斥反应的体液成分可能代表了与细菌和其他感染因子共享抗原表位的异种靶抗原对这种类型的B细胞抗体应答的刺激。
The early phases of the rejection of xenografts exchanged between closely related species are dominated by a vigorous humoral immune response. We have recently used a linker-mediated polymerase chain reaction (LM-PCR) to generate Ig heavy and light chain-specific cDNA libraries to examine the Ig gene control of a prototypic IgM monoclonal antibody, HAR-1, that causes the hyperacute rejection of hamster xenografts. Recombinant clones from the library were screened directly from bacterial colonies by PCR and the nucleic acid sequences of the clones established, Our results demonstrate that the HAR-1 hybridoma is encoded by Ig V-H and J(H) genes in a germline configuration, Comparison of the cDNA sequence for HAR-1 V-H with the germline equivalent of this gene isolated from newborn LEW liver (provisionally designated V(H)HAR-1) showed that the two V-H sequences share a nucleic acid identity of 99.3%. Similarly, the HAR-1 monoclonal uses a Ig J(H) gene that is 98.2% identical with the J(H)1 nucleic acid sequence available in the GeneBank. The use of Ig V-H and J(H) genes in a germline configuration is similar to that seen with polyreactive natural antibodies to infectious agents and autoantibodies. These humoral responses are thought to be the result of the stimulation of a T cell-independent subset of B cells, the B-1a/B-1b subset, that is responsible for producing antibodies that serve as a primitive humoral (natural antibody) defense mechanism against infectious diseases. Our results suggest that the humoral component of the rejection of xenografts in the hamster-to-rat model may represent the stimulation of this type of B cell antibody response by xenogeneic target antigens that share antigenic epitopes with bacteria and other infectious agents.