Pathogenesis of CLL subsets. The 2 major subsets (U-CLL and M-CLL) and the isotype-switched variant derive from 3 different normal B-cell populations with no interconversion. Infection is the likely initial drive on all, with transformation to U-CLL occurring before initiation of somatic mutation. M-CLL and isotype-switched CLL develop from more mature B cells presumed to have undergone antigen selection in the germinal center.