Davey M P, Starkebaum G, Loughran T P
Department of Medicine, Oregon Health Sciences University, Portland.
Blood. 1995 Jan 1;85(1):146-50.
CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology characterized by clonal proliferation of T cells that usually express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diversity (D) region TCR beta-chain genes expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the etiology of this disorder. Twelve patients with LGL leukemia were studied, including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown etiology that occurs frequently in patients with LGL leukemia. Clonally expanded T cells that express specific TCR V beta genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, V beta expression was determined by PCR using a panel of 22 unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant V beta gene product was readily apparent in all patients. To confirm that the dominant V beta gene originated from a clonal expansion, DNA fragments corresponding to the dominant V beta genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The V beta and J beta genes expressed by the leukemic cells showed a pattern of distribution that followed the frequency with which these genes are represented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR beta chain were different in all cases. A specific pattern of VDJ usage was not identified for those patients with both LGL leukemia and RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed only in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been clonally transformed in a random fashion with respect to the TCR beta chain.
CD3⁺大颗粒淋巴细胞（LGL）白血病是一种病因不明的疾病，其特征为通常表达T细胞受体（TCR）αβ异二聚体的T细胞发生克隆性增殖。本研究的目的是鉴定CD3⁺LGL白血病细胞表达的可变（V）、连接（J）和多样性（D）区域TCRβ链基因，以期深入了解该疾病的病因。对12例LGL白血病患者进行了研究，其中7例同时患有LGL白血病和类风湿关节炎（RA）。RA也是一种病因不明的疾病，在LGL白血病患者中经常出现。在RA患者关节的体液和组织标本中已鉴定出表达特定TCR Vβ基因的克隆性扩增T细胞。在本研究中，使用一组22种独特的Vβ引物通过PCR来扩增从外周血单个核细胞（PBMC）制备的cDNA，从而确定Vβ表达。在所有患者中，一种占主导地位的Vβ基因产物很容易被检测到。为了确认占主导地位的Vβ基因源自克隆性扩增，将与占主导地位的Vβ基因相对应的DNA片段亚克隆到质粒中，并对独立分离的重组体进行测序。重复出现的V-D-J区域序列表明存在克隆性。白血病细胞表达的Vβ和Jβ基因呈现出一种分布模式，该模式与这些基因在外周血中的出现频率一致。在所有病例中，与TCRβ链第三个互补决定区相对应的残基均不同。对于同时患有LGL白血病和RA的患者，未发现特定的VDJ使用模式；然而，仅在RA的情况下观察到LGL克隆（N = 3）对Vβ-6的利用。这些数据表明，白血病性CD3⁺LGL细胞在TCRβ链方面已以随机方式发生克隆性转化。
