Seifert Marc, Scholtysik René, Küppers Ralf
Institute of Cell Biology (Cancer Research), Medical School, University of Duisburg-Essen, Nordrhein-Westfalen, Essen, Germany.
Methods Mol Biol. 2019;1956:1-33. doi: 10.1007/978-1-4939-9151-8_1.
Immunoglobulin (IG) gene remodeling by V(D)J recombination plays a central role in the generation of normal B cells, and somatic hypermutation and class switching of IG genes are key processes during antigen-driven B cell differentiation. However, errors of these processes are involved in the development of B cell lymphomas. IG locus-associated translocations of proto-oncogenes are a hallmark of many B cell malignancies. Additional transforming events include inactivating mutations in various tumor suppressor genes and also latent infection of B cells with viruses, such as Epstein-Barr virus. Many B cell lymphomas require B cell antigen receptor expression, and in several instances, chronic antigenic stimulation plays a role in lymphoma development and/or sustaining tumor growth. Often, survival and proliferation signals provided by other cells in the microenvironment are a further critical factor in lymphoma development and pathophysiology. Many B cell malignancies derive from germinal center B cells, most likely because of the high proliferation rate of these cells and the high activity of mutagenic processes.
通过V(D)J重组进行的免疫球蛋白(IG)基因重塑在正常B细胞的产生中起核心作用，IG基因的体细胞超突变和类别转换是抗原驱动的B细胞分化过程中的关键步骤。然而，这些过程的错误与B细胞淋巴瘤的发生有关。IG基因座相关的原癌基因易位是许多B细胞恶性肿瘤的标志。其他转化事件包括各种肿瘤抑制基因的失活突变以及B细胞被病毒（如爱泼斯坦-巴尔病毒）的潜伏感染。许多B细胞淋巴瘤需要B细胞抗原受体表达，在某些情况下，慢性抗原刺激在淋巴瘤发展和/或维持肿瘤生长中起作用。通常，微环境中其他细胞提供的生存和增殖信号是淋巴瘤发展和病理生理学中的另一个关键因素。许多B细胞恶性肿瘤起源于生发中心B细胞，很可能是因为这些细胞的高增殖率和诱变过程的高活性。
