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Immunogenetic analysis of the B cell receptors (BcRs) has been a richly rewarding field for unraveling the pathogenesis of human lymphomas, including CLL. A biased immunoglobulin gene repertoire is seen as evidence for selection of CLL progenitor cells by antigen. Additional corroborative evidence is provided by the differential prognosis of cases with distinct mutational status of the clonotypic BcRs. However, perhaps the strongest immunogenetic “evidence for the importance of interactions with microenvironment in driving CLL development and evolution is the existence of subsets of patients with quasi-identical, stereotyped BcRs, collectively accounting for a remarkable one-third of the entire cohort. These observations have been instrumental in shaping the notion that CLL ontogeny is functionally driven and dynamic, rather than a simple stochastic process. From a clinical perspective, ample evidence indicates that immunogenetic information can be used for the biologically and clinically rational categorization of CLL, with important potential implications for basic, translational and clinical research.