Abe Satoshi
Department of Molecular Neuropathology, Brain Research Institute, Niigata University.
Rinsho Shinkeigaku. 2002 Nov;42(11):1124-6.
A semi-nested polymerase chain reaction for the variable region of the immunoglobulin heavy and light chain genes (VH, V kappa and V lambda) was used to investigate the cell of origin and the clonal history in intravascular malignant lymphomatosis (IML), primary central nervous system lymphoma (PCNSL) and diffuse large B-cell lymphoma (DLBCL). A monoclonal band of VH and V kappa genes was detected in all cases of IML. A monoclonal band of VH was also detected in PCNSL and DLBCL. The nucleotide sequences of the VH and V kappa genes were determined. Numerous point mutations were present in all of the VH and V kappa genes. Ongoing mutation was observed in 3 of 5 IML cases, in 1 of 5 PCNSL and in 4 of 12 DLBCL. Because the process of immunoglobulin gene hypermutation is thought to occur at the germinal center (GC) stage of B cell development, these results suggest that IML, PCNSL and DLBCL are derived from GC B cells or their descendants. Using this reliable and sensitive method, a monoclonal band was detected in peripheral blood samples from 5 IML cases. The diagnosis of IML was confirmed by biopsies or autopsies in 4 cases. The sequences obtained from biopsied tissues and blood samples were found to be identical in each case in 3 cases examined.
采用针对免疫球蛋白重链和轻链基因可变区(VH、Vκ和Vλ)的半巢式聚合酶链反应,来研究血管内恶性淋巴瘤(IML)、原发性中枢神经系统淋巴瘤(PCNSL)和弥漫性大B细胞淋巴瘤(DLBCL)的起源细胞及克隆史。在所有IML病例中均检测到VH和Vκ基因的单克隆条带。在PCNSL和DLBCL中也检测到VH的单克隆条带。测定了VH和Vκ基因的核苷酸序列。所有VH和Vκ基因中均存在大量点突变。在5例IML中的3例、5例PCNSL中的1例以及12例DLBCL中的4例中观察到正在进行的突变。由于免疫球蛋白基因超突变过程被认为发生在B细胞发育的生发中心(GC)阶段,这些结果提示IML、PCNSL和DLBCL源自GC B细胞或其后代。使用这种可靠且灵敏的方法,在5例IML病例的外周血样本中检测到单克隆条带。4例经活检或尸检确诊为IML。在3例检测的病例中,发现从活检组织和血样获得的序列在每个病例中均相同。