Recent research has revealed the existence of subsets (clusters) of patients with different types of B-cell lymphomas and leukemias with restricted, “stereotyped” immunoglobulin (IG) variable heavy complementarity-determining region 3 (VH CDR3) sequences within their B cell receptors (BcR), suggesting selection by common epitopes or classes of structurally similar epitopes. BcR stereotypy was initially described in chronic lymphocytic leukemia (CLL), where it constitutes a remarkably frequent feature of the IG repertoire, and subsequently identified in other malignancies, including mantle cell lymphoma and splenic marginal-zone lymphoma. Of note, at least in CLL, emerging evidence indicates that the grouping of cases into distinct clusters with stereotyped BcR is functionally and prognostically relevant. Hence, the reliable identification of BcR stereotypy may assist in the investigation of the nature of the selecting antigens and immune pathways leading to lymphoma development, and also potentially pave the way for tailored treatment strategies applicable to each major stereotyped subset. In this chapter, we provide an overview of BcR stereotypy in human B-cell malignancies, and outline previous and current methodological approaches used for its identification.
