A peculiar finding in early immunogenetic studies of the IG repertoire in CLL was that unrelated CLL cases could carry highly similar VH CDR3s characterized by shared amino acid motifs.16,17 This was confirmed by the landmark study by Chiorazzi’s group, who reported the existence of subsets of BCR IGs with highly restricted VH CDR3s and proposed that a common antigen could be selecting out clones eventually leading to the observed restrictions.28 This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.