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人类B细胞肿瘤对免疫球蛋白重链可变区基因的差异使用情况。

Differential usage of an Ig heavy chain variable region gene by human B-cell tumors.

作者信息

Stevenson F K, Spellerberg M B, Treasure J, Chapman C J, Silberstein L E, Hamblin T J, Jones D B

机构信息

Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, UK.

出版信息

Blood. 1993 Jul 1;82(1):224-30.

PMID:8324224
Abstract

A monoclonal anti-idiotypic antibody has been raised that recognizes Igs with heavy chains encoded by a member of the VH4 family, the VH4-21 gene segment. The idiotope (Id) is detectable on a high percentage of early B cells in fetal spleen, and is expressed by certain autoantibodies, particularly cold-reactive anti-red blood cell antibodies. Therefore, it was of interest to investigate usage of this VH gene by neoplastic B cells; 81 chronic lymphocytic leukemias (CLLs) involving CD5+ B cells and 62 B-cell lymphomas of varying histologic type have been analyzed. The Id was expressed by only 3 of 81 (3.7%) of the CLLs, indicating a relatively low usage by these tumors. In contrast, the Id was expressed by 9 of 62 (14.5%) of the lymphomas across a range of histologic types, indicating a differential use of the VH4-21 gene among B-cell neoplasms. For three of the Id-positive lymphomas, each of a different histologic class, the nucleotide sequence of the tumor-derived VH gene was determined; the VH4-21 gene was identified, as expected. The sequence from the CLL was identical to the germline sequence, and the marginal zone lymphoma showed only 3 nucleotide changes, 2 of which gave rise to amino acid substitutions. In contrast, the sequence from the follicular lymphoma showed 29 nucleotide changes giving rise to 14 amino acid substitutions, which were scattered among the CDR and FW regions.

摘要

已制备出一种单克隆抗独特型抗体,该抗体可识别由VH4家族成员VH4-21基因片段编码重链的免疫球蛋白。这种独特型表位(Id)在胎儿脾脏中高比例的早期B细胞上可检测到,并且某些自身抗体,特别是冷反应性抗红细胞抗体也可表达该表位。因此,研究肿瘤性B细胞对这种VH基因的使用情况很有意义;已对81例累及CD5+B细胞的慢性淋巴细胞白血病(CLL)和62例不同组织学类型的B细胞淋巴瘤进行了分析。在81例CLL中只有3例(3.7%)表达Id,表明这些肿瘤对该基因的使用相对较少。相比之下,在62例淋巴瘤中有9例(14.5%)表达Id,这些淋巴瘤涵盖了多种组织学类型,表明B细胞肿瘤对VH4-21基因的使用存在差异。对于3例Id阳性淋巴瘤(每例属于不同的组织学类别),测定了肿瘤来源的VH基因的核苷酸序列;正如预期的那样,鉴定出了VH4-21基因。来自CLL的序列与种系序列相同,边缘区淋巴瘤仅显示3个核苷酸变化,其中2个导致氨基酸替换。相比之下,来自滤泡性淋巴瘤的序列显示29个核苷酸变化,导致14个氨基酸替换,这些替换分散在互补决定区(CDR)和构架区(FW)。

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Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance.固有自身反应性VH4-34 B细胞在维持人类B细胞耐受性中的调控。
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Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
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J Clin Invest. 1998 Oct 15;102(8):1515-25. doi: 10.1172/JCI3009.
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