Mixed Phenotype Lymphomas in Thymectomized (SL/KhxAKR/Ms)F1 Mice

Abstract

Lymphomagenesis in mice is determined both by genetic and epigenetic mechanisms. The inbred strain SL/Kh mice selectively develop pre‐B lymphomas and AKR/Ms, T‐lymphomas. In crosses between SL/Kh and AKR/Ms, an AKR‐derived dominant gene Tlsm1 (Thymic lymphoma susceptible mouse‐1) determines the type of lymphoma to be a T‐lymphoma. As an approach to the role of Tlsm1, we studied the effect of thymectomy at 1 week of age in (SL/KhxAKR/Ms)Fl hybrids. In intact F1 mice, the predominant type of lymphoma was of T‐lineage, whereas in thymectomized mice, it was an unusual mixed‐phenotype lymphoma. They were basically CD5+ B‐lymphomas with a rearranged immunoglobulin gene, but carried NK1 and Mac1 on the cell surface and large lysosomal granules in the cytoplasm. Histologically, the lymphoma consisted of large lymphoblastoid cells and infiltrated the spleen, lymph node and liver. Electron microscopy and histochemistry revealed numerous cytoplasmic granules containing acid phosphatase and lysozyme. These morphological features are suggestive of large granular lymphocytes. They expressed interleukin‐4, perforin, and interferon‐γ. On transplantation, these lymphoma cells grew equally well in intact and thymectomized F1 recipients.

Pre‐B lymphomas in SL/Kh mice: A multifactorial disease model

“…In intact (SL/Kh×AKR)F1, the predominant type of tumor is the T lymphoma, whereas, when the F1 mice are thymectomized at 3-5 days of age, lymphomas with an unusual phenotype arise at an incidence >90%. 22) These lymphomas express NK1 and have cytoplasmic granules, which are similar to large granular lymphocytes. Interestingly, they express B220, CD5, surface IgM, CD16, and Mac1, but not CD3, CD4, CD8, or Thy1.1.…”