The BCRs associated with class-switched isotypes within the CLL clones (IgA1/2, IgE, IgG1/2, and IgG3) had a greater number of SHMs away from the central CLL BCR in all CLL patients sampled compared to IgM/D, suggesting a coupled process of SHM and B-cell class-switching in the malignant clone (Figure 3B). Here, IGHE is linked to B-cell chronic lymphocytic leukemia.