CDR-deleted mice develop CLL. (A) Flow cytometry of PBMC (PB), splenic (Sp), or BM cells from a mouse presenting with CLL/small cell lymphocytic leukemia (SLL) and a wild-type (WT) mouse as control for CD5 and the B-cell marker B220 (top), IgM and IgD (middle), and eGFP and B220 (bottom). The CLL/SLL case shows a predominant CD5+B220lo population in the spleen and PB that was IgMhiIgD+/low and eGFP+, demonstrating that the tumor clone is indeed derived from a CDR-deleted B cell. (B) Representative H&E–stained spleen, BM, and liver sections from CDR-deleted mice presenting with CLL/SLL (right) and an age-matched WT mouse (left). CLL/SLL section shows enlargement of the splenic white pulp by the expansion or accumulation of small B cells with architectural and morphologic features of CLL/SLL (top), aggregates of small lymphocytes in the BM (middle) and liver (bottom). Both flow cytometric and histological analysis were performed for all mice of the 15- to 18-month-old CDR cohort (for numbers of mice analyzed, see Figures 4 and 5; for details regarding micrographs, see “Cell isolation, flow cytometry, and histology”).