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交叉反应性人类淋巴瘤独特型

Crossreacting human lymphoma idiotypes.

作者信息

Rudders R A, Levin A, Jespersen D, Zacks J, Delellis R, Ranger A, Krontiris T

机构信息

Department of Medicine, Tufts University School of Medicine, Boston, MA.

出版信息

Blood. 1992 Aug 15;80(4):1039-44.

PMID:1379849
Abstract

We have examined an unselected series of 72 lymphomas of diverse histologies with a panel of mouse monoclonal antibodies specific for human B-lymphoma-derived Ig idiotypes (anti-ids) to determine the nature and extent of id/anti-id crossreactivity. The anti-id antibodies were prepared from Ig isolated from seven follicular center cell lymphomas by heterohybridoma technique. Thirty-six of 75 individual anti-ids obtained in this manner were further selected based on their reactivity with highly restricted or private idiotypic determinants. Twelve of the 72 (17%) lymphoma biopsies reacted with one or more of the 36 anti-ids that detect private determinants. A pool consisting of five individual antibodies would have detected 11 of the 12 crossreacting tumors. Staining of tumor cell populations was homogeneous in the positive cases, suggesting uniform idiotype expression. If there was a segregated staining pattern, it was generally related to the presence of CD3+ T cells in the section. These follicular center cell-derived anti-ids cross-reacted with follicular center cell tumors of all histologic grades with frequencies ranging from 13% to 50%. The structural basis for the crossreactivity of our lymphoma-derived private anti-ids is as yet not known. However, the reactivity of certain anti-ids with both kappa- and lambda-expressing tumors suggests a biased use of V gene segments in these crossreactive clones that is probably related to the VH gene. These data suggest the possibility that lymphoma may develop in a highly restricted pool of normal differentiated B cells or in B-cell subsets that express a limited repertoire of unmutated VH gene segments.

摘要

我们用一组针对人B淋巴瘤来源的Ig独特型的小鼠单克隆抗体(抗独特型抗体)检测了72例未经选择的不同组织学类型的淋巴瘤,以确定独特型/抗独特型交叉反应的性质和程度。抗独特型抗体是通过异种杂交瘤技术从7例滤泡中心细胞淋巴瘤分离的Ig制备的。以这种方式获得的75个个体抗独特型抗体中,有36个基于它们与高度受限或私有独特型决定簇的反应性被进一步筛选。72例淋巴瘤活检中有12例(17%)与检测私有决定簇的36种抗独特型抗体中的一种或多种发生反应。由5种个体抗体组成的混合物可检测出12例交叉反应肿瘤中的11例。在阳性病例中,肿瘤细胞群体的染色是均匀的,表明独特型表达一致。如果存在分离的染色模式,通常与切片中CD3+T细胞的存在有关。这些滤泡中心细胞来源的抗独特型抗体与所有组织学分级的滤泡中心细胞瘤发生交叉反应,频率范围为13%至50%。我们淋巴瘤来源的私有抗独特型抗体交叉反应的结构基础尚不清楚。然而,某些抗独特型抗体与表达κ链和λ链的肿瘤均有反应,这表明在这些交叉反应克隆中V基因片段的使用存在偏差,这可能与VH基因有关。这些数据提示淋巴瘤可能在正常分化的B细胞高度受限的群体中或在表达有限未突变VH基因片段库的B细胞亚群中发生。

相似文献

1
Crossreacting human lymphoma idiotypes.交叉反应性人类淋巴瘤独特型
Blood. 1992 Aug 15;80(4):1039-44.
2
Clonal diversity in human B cell lymphoma. I. Idiotypic and genetic analysis of lymphoma heterohybrids.人类B细胞淋巴瘤中的克隆多样性。I. 淋巴瘤异种杂交瘤的独特型和遗传学分析。
J Immunol. 1990 Jan 1;144(1):396-407.
3
The targeting of CD4+ T lymphocytes to a B cell lymphoma. A comparison of anti-CD3-anti-idiotype antibody conjugates and antigen-anti-idiotype antibody conjugates.CD4+ T淋巴细胞对B细胞淋巴瘤的靶向作用。抗CD3-抗独特型抗体偶联物与抗原-抗独特型抗体偶联物的比较。
J Immunol. 1989 Jun 1;142(11):4079-84.
4
Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma.慢性淋巴细胞白血病和B细胞淋巴瘤的共享独特型表达。
Blood. 1990 Nov 1;76(9):1825-9.
5
Idiotypic analysis of anti-I-Ak monoclonal antibodies. III. T- and B-cell responses to anti-Ia idiotopes are not modulated by syngeneic anti-idiotypic monoclonal antibodies.抗I-Ak单克隆抗体的独特型分析。III. 针对Ia独特型的T细胞和B细胞反应不受同基因抗独特型单克隆抗体的调节。
Cell Immunol. 1985 Dec;96(2):363-75. doi: 10.1016/0008-8749(85)90367-3.
6
Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas.针对人类B细胞淋巴瘤产生单克隆抗独特型抗体的策略。
J Immunol. 1984 Jul;133(1):495-501.
7
Idiotypic analysis of monoclonal anti-fluorescyl antibodies: localization and characterization of idiotypic determinants.单克隆抗荧光素抗体的独特型分析:独特型决定簇的定位与特性
Mol Immunol. 1983 Dec;20(12):1301-12. doi: 10.1016/0161-5890(83)90161-x.
8
Monoclonal anti-Id antibodies react with varying proportions of human B lineage cells.单克隆抗独特型抗体与不同比例的人B淋巴细胞系细胞发生反应。
J Immunol. 1987 Jun 15;138(12):4150-8.
9
Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. I. Role of idiotypic immunoglobulin.针对B细胞肿瘤诱导同基因细胞毒性T淋巴细胞。I. 独特型免疫球蛋白的作用。
Cell Immunol. 1992 Jun;142(1):54-66. doi: 10.1016/0008-8749(92)90268-t.
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Bispecific anti-idiotype/anti-CD3 antibody therapy of murine B cell lymphoma.鼠源B细胞淋巴瘤的双特异性抗独特型/抗CD3抗体疗法。
J Immunol. 1991 Dec 1;147(11):4035-44.

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