Hatzivassiliou G, Miller I, Takizawa J, Palanisamy N, Rao P H, Iida S, Tagawa S, Taniwaki M, Russo J, Neri A, Cattoretti G, Clynes R, Mendelsohn C, Chaganti R S, Dalla-Favera R
Institute of Cancer Genetics, Columbia University, New York, NY 10032, USA.
Immunity. 2001 Mar;14(3):277-89. doi: 10.1016/s1074-7613(01)00109-1.
Abnormalities of chromosome 1q21 are common in B cell malignancies, but their target genes are largely unknown. By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families. Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the immunoglobulin Calpha domain to produce a chimeric IRTA1/Calpha fusion protein. In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated. Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development and lymphomagenesis.
1q21染色体异常在B细胞恶性肿瘤中很常见,但其靶基因大多未知。通过克隆骨髓瘤细胞系中(1;14)(q21;q32)染色体易位的断点,我们鉴定出两个新基因IRTA1和IRTA2,它们编码与Fc和抑制性受体家族同源的细胞表面受体。这两个基因在成熟B细胞中选择性表达:IRTA1在边缘区B细胞中表达,IRTA2在中心细胞、边缘区B细胞和成免疫细胞中表达。由于t(1;14),IRTA1与免疫球蛋白Cα结构域融合,产生嵌合的IRTA1/Cα融合蛋白。在具有1q21异常的肿瘤细胞系中,IRTA2表达失调。因此,IRTA1和IRTA2是参与B细胞发育和淋巴瘤发生的新型免疫受体。