Nakamura Naoya, Abe Masafumi
Department of Pathology I, Fukushima Medical University School of Medicine, Fukushima, Japan.
Fukushima J Med Sci. 2003 Dec;49(2):55-67. doi: 10.5387/fms.49.55.
The immunoglobulin heavy chain (IgH) gene of B-cells dramatically alters twice in their differentiation to memory or plasma cells; VDJ recombination at B-cell precursor and somatic hypermutation, class switch recombination and receptor revision at germinal center (GC) B-cells. Among them, somatic hypermutation of the IgH gene variable region (VH gene) is a powerful tool for detection of B cell differentiation. B-cells and B-cell neoplasms have been divided into following; 1) pre-GC B-cells and neoplasms with a germline VH gene and 2) GC and post-GC B-cells and neoplasms with a somatically mutated VH gene. In this article, we review normal B-cell differentiation and histogenesis of various types of B-cell neoplasms on the aspect of somatic mutation of the rearranged VH gene. In particular, differences between CD5+ and CD5- B-cell neoplasms, using our own data of over 100 cases with B-cell neoplasms, are discussed. Although CD5+ B-cells are included in pre-GC B-cells for the reason of germline VH gene in most of CD5+ B-cells, an about 5% of CD5+ B-cells show somatically mutated VH gene. The rearranged VH gene of CD5+ B-cell neoplasms shows heterogeneity, whereas CD5- B-cell neoplasms possess somatically mutated VH gene with a mean of 8 approximately 12%. Both CD5+ B-cell chronic lymphocytic leukemia and CD5+ diffuse large B-cell lymphoma display that about half of cases show a germline or low frequency of somatic mutation and the others possess somatically mutated VH gene. CD5+ mantle cell lymphoma constitutes most cases with germline and a small number of cases with mutated VH gene. Therefore, CD5- B-cells & CD5- B-cell neoplasms are distinct from CD5+ B-cells and CD5+ B-cell neoplasms in somatic mutation of VH gene. It suggests that each of CD5- and CD5+ B-cells independently has its own differentiation.
B细胞的免疫球蛋白重链（IgH）基因在其分化为记忆细胞或浆细胞的过程中会发生两次显著变化；在B细胞前体阶段发生VDJ重组，在生发中心（GC）B细胞阶段发生体细胞超突变、类别转换重组和受体编辑。其中，IgH基因可变区（VH基因）的体细胞超突变是检测B细胞分化的有力工具。B细胞和B细胞肿瘤可分为以下两类：1）前GC B细胞和具有种系VH基因的肿瘤，以及2）GC和GC后B细胞和具有体细胞突变VH基因的肿瘤。在本文中，我们从重排的VH基因体细胞突变的角度综述了正常B细胞分化和各类B细胞肿瘤的组织发生。特别是，利用我们自己超过100例B细胞肿瘤的数据，讨论了CD5+和CD5- B细胞肿瘤之间的差异。尽管由于大多数CD5+ B细胞具有种系VH基因，CD5+ B细胞被归入前GC B细胞，但约5%的CD5+ B细胞显示体细胞突变的VH基因。CD5+ B细胞肿瘤的重排VH基因表现出异质性，而CD5- B细胞肿瘤具有体细胞突变的VH基因，平均比例约为8%至12%。CD5+ B细胞慢性淋巴细胞白血病和CD5+弥漫性大B细胞淋巴瘤均显示，约一半的病例表现为种系或体细胞突变频率较低，其余病例具有体细胞突变的VH基因。CD5+套细胞淋巴瘤大多数病例为种系，少数病例为突变的VH基因。因此，CD5- B细胞和CD5- B细胞肿瘤在VH基因的体细胞突变方面与CD5+ B细胞和CD5+ B细胞肿瘤不同。这表明CD5-和CD5+ B细胞各自独立地有其自身的分化过程。
