Fig. 3: Accumulation of abnormal B lymphocytes in Eµ-MTCP1 mice.

A Representative gross images of severely enlarged spleens from Z36 and Z20 founder Eµ-MTCP1 mice, an observation consistently observed in subsequent progeny comprising the Eµ-MTCP1 colonies. A representative gross image of a healthy spleen from an age-matched wildtype mouse is shown for comparison. Scale bar is 1 cm. B Post-mortem histopathology analysis of cervical lymph nodes, bone marrow, and spleen from Eµ-MTCP1 founder mice Z36 and Z20 with CLL-like disease show histologic changes in multiple tissues consistent with a systemically disseminated mixed neoplasm containing B-lymphocytes and histiocytes. Lymphocytes were typically B220⁺, indicating a B-cell origin. CD3⁺ lymphocytes were sometimes scattered throughout the neoplasm and may be tumor infiltrating lymphocytes. Histiocytoid cells were identified as F4/80 positive in most cases. Cells null for B220, CD3, and F4/80 were occasionally observed. Z36 images representative of n = 7 evaluated mice, Z20 images representative of n = 3 evaluated mice. All organs visualized at 60x, scale bars are 33.3 µm. C Representative immunophenotypic evaluation of B-cell populations in blood derived from Eµ-MTCP1 (Z20 at ERC, 9 months old), Eµ-TCL1 (at ERC, 12 months old) and wildtype mice (12 month old). CD3⁺ T and CD11b⁺ myeloid cells were gated out and cells were plotted using CD19 and CD5 expression markers to identify CD19⁺CD5⁺ population (CLL-like cells) and CD19⁺CD5⁻ (maturing B cells). CD19⁺CD5⁺ population were further dissected according to CD21 and IgM expression to identify CD21⁺IgM⁺ marginal zone/marginal zone progenitor (MZ/MZP) B cells, CD21^intIgM^dim follicular B cells, CD21⁻IgM⁻ and CD21⁻IgM⁺ atypical B cells. CLL-like cells were also evaluated for IgD and CD23 expression. Overall, the malignant cells of Eμ-MTCP1 mice showed a CD19⁺CD5⁺CD93⁻B220^dim phenotype with dim surface expression of IgM, IgD, and CD23 confirming a B1a cell phenotype.