Early commitment to neoplasia in murine B- and T-cell lymphomas arising late in life

Lymphomas arise spontaneously in C57BL/10.H-2aH-4b (2a4b) mice greater than 1 year old. The purpose of this study was to determine when cells become committed to neoplasia and whether genes linked to H-2a or H-4b are a factor in predisposition to genesis of lymphoma. Following transplantation of a pool of spleen cells in large groups of mice, lymphoma incidence increased 1.8- to 2.1-fold and mean latent periods decreased, compared with those in controls. Lymphomas arising in mice that received the same pool of spleen cells often displayed identical rearrangements of genes for immunoglobulin and T-cell receptor. This finding indicates that the lymphomas were derived from expanding clones of cells present in the donor mice prior to transfer. The age of the donor mice determined the latency of lymphomas arising after spleen cell transfer. When donors were 3-4 months old at the time of spleen cell transfer, lymphomas were detected in the recipients 1 year later. When mice 1.5-2 years old were used as donors, tumors were observed 3 months after transfer. Almost all of these tumors were clonally related B-cell lymphomas. We conclude that the lymphomas seen late in life arise from premalignant clones of cells that have become committed to neoplasia in relatively young animals. These clones normally follow an indolent course and are manifested clinically only in old age. Neither H-2a nor H-4b alone appeared to alter susceptibility to the genesis of lymphoma in similar experiments with H-2a and H-4b congenic mice.