The expressed heavy chain V gene repertoire of circulating B cells in normal adults.

The expressed heavy chain V gene repertoire of circulating B cells in normal adults.
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正常成人循环 B 细胞表达的重链 V 基因库。

DOI:
10.1111/j.1749-6632.1995.tb55836.x
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发表时间:
1995
影响因子:
5.2
通讯作者:
Stollar,BD
Stollar,BD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stollar,BD

文献摘要

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对表达的人类免疫球蛋白谱系的分析有几个目的。对胎儿、新生儿和成人的曲目进行比较,探索免疫系统的发育程序,询问个体的不同免疫反应能力是如何发展的,以及不同人之间的差异。如何在有或没有突变的大量潜在的基因片段组合中做出选择?对病毒或细菌抗原的特定抗体反应是如何从暴露于这种环境抗原之前形成的主要谱系中产生的?人们如何评估在恶性肿瘤和自身免疫中出现的V基因片段使用的限制模式?疾病相关自身抗体和出现在主要曲目中的自然自身抗体之间有什么关系?骨髓瘤蛋白的一级结构数据中存在反映全谱表达的早期信息。随后,重排的基因组DNA的序列数据积累了,更多的来自人类杂交瘤、EBV转化的B细胞和白血病B细胞的Ig cDNA的序列数据积累了。选择许多杂交瘤和病毒转化的B细胞进行研究,主要是因为它们的产品是感兴趣的-自身抗体或抗细菌或病毒抗原的抗体。此外,还对胎儿和新生儿B细胞的DNA进行了分析,可分析数量有限的单个杂交瘤和EBV转化的细胞。为了检测更多的细胞,用特异性探针1-12和PCRE,13-‘5进行原位杂交,既用于胎儿和成人B细胞群体,也用于H链和L链。同时,在确定V区片段16-2‘的基因组含量方面取得的进展,对于解释在重排DNA、mRNA和蛋白质水平上获得的序列数据至关重要。
Analyses of the expressed human Ig repertoire are undertaken for several purposes. Comparisons of fetal, neonatal, and adult repertoires explore the developmental program of the immune system, asking how the capacity for diverse immune responses develops in an individual and how it varies among different persons. How are choices made among the vast numbers of potential combinations of gene segments with or without mutations? How do particular antibody responses to viral or bacterial antigens arise from a primary repertoire formed before exposure to such environmental antigens? How does one evaluate restricted patterns of V gene segment usage seen in malignancy and autoimmunity? What is the relationship between disease-associated and natural autoantibodies that appear in a primary repertoire? Early information reflecting repertoire expression was present in primary structure data for myeloma proteins.'Subsequently, there has been an accumulation of sequence data for rearranged genomic DNA, and even more for Ig cDNA from human hybridomas, EBV-transformed B cells, and leukemic B cell^.^-^ Many hybridomas and virus-transformed B cells were chosen for study mainly because their products were of interest-either autoantibodies or antibodies to bacterial or viral antigens. In addition, cDNAs from fetal and neonatal B cells were analyzed in studies of repertoire deve I~ pment.~-~ Limited numbers of individual hybridomas and EBV-transformed cells can be analyzed. For examination of larger numbers of cells, in situ hybridization with specific probes1-12 and PCRE, 13-'5 have been applied to both fetal and adult B-cell populations and to both H and L chains. Simultaneous advances in defining the genomic content of V region segments16-2'have been of paramount importance for interpretation of sequence data obtained at the levels of rearranged DNA, mRNA, and protein.