B Cell Neoplasia Unit, Istituto Scientifico San Raffaele, Milan, Italy.
Adv Exp Med Biol. 2013;792:1-24. doi: 10.1007/978-1-4614-8051-8_1.
Nowadays, chronic lymphocytic leukemia (CLL) is considered as a prototypic antigen-driven lymphoma, with antigenic stimuli from the microenvironment promoting tumor outgrowth. Antigen recognition is a function of both the clonotypic B cell receptor immunoglobulin (BcR IG) and various other immune sensors, e.g., the Toll-like receptors. The critical role of BcR IG-mediated signaling in CLL development and evolution is underscored by the following: the disease-biased IG gene repertoire; the subdivision of CLL based on the somatic hypermutation load of the BcR IG into two broad categories with vastly different prognosis and eventual outcome; the existence of subsets of cases with distinct, quasi-identical (stereotyped) BcR IGs; and the clinical efficacy of novel therapeutics inhibiting BcR signaling. Here, we trace the immunogenetic evidence for antigen selection in CLL and also consider the types of implicated antigens as well as the immune signaling pathways relevant for CLL ontogeny and clonal progression.
目前，慢性淋巴细胞白血病（CLL）被认为是一种典型的抗原驱动性淋巴瘤，其肿瘤生长受到微环境中抗原刺激的促进。抗原识别是克隆型 B 细胞受体免疫球蛋白（BcR IG）和各种其他免疫传感器（例如 Toll 样受体）的功能。BcR IG 介导的信号转导在 CLL 发展和演进中的关键作用体现在以下几个方面：疾病偏向的 IG 基因库；根据 BcR IG 的体细胞超突变负荷将 CLL 分为两个广泛的类别，预后和最终结果截然不同；存在具有明显、准同源（定型）BcR IG 的病例亚群；以及抑制 BcR 信号的新型治疗药物的临床疗效。在这里，我们追溯了 CLL 中抗原选择的免疫遗传学证据，同时也考虑了相关的抗原类型以及与 CLL 个体发生和克隆进展相关的免疫信号通路。
