Isolation and Characterization of a Murine Spontaneous High-Grade Follicular Lymphoma with Restricted In Vivo Spreading - a Model for Lymphatic Metastasis Via the Mesentery

Spontaneous or induced malignant lymphomas in mice are valuable tools for studying human lymphoproliferative diseases, including the mechanism of migration between peripheral lymphoid organs and positioning within distinct tissue compartments. Here we report the isolation and characterization of a novel spontaneous lymphoma from BALB/c mice showing restricted tissue distribution and metastasis. The lymphoma cells display CD19, B220, MHC II, surface IgG2a/kappa chain with V(H)7183 rearrangement of the IgH gene, indicating their B-cell origin. Serial intraperitoneal injection of primary tumor into both BALB/c and RAG-1-deficient hosts led to the successful propagation of lymphoma. Despite the cytological characteristics of high-grade follicular B-cell lymphoma, the tumor cells (denoted as Bc-DLFL. 1) showed significantly lesser spreading to extraabdominal locations upon intraperitoneal passage compared to splenic and mesenteric lymph node expansion. In mesenteric lymph nodes the high endothelial venules contained only few tumor cells, while the lymphatic vessels were almost completely filled with lymphoma cells. Similarly, the LYVE-1-positive lymphatic capillaries within the mesentery were packed with lymphoma cells. These findings suggest that Bc-DLFL. 1 cells likely propagate primarily via the lymphatic circulation within the mesentery, therefore this tumor may offer an in vivo model to investigate the tumor cell migration via the lymphatic circulation from the peritoneal cavity.