Mixed phenotype lymphomas of B10.H-2a-H-4bp/Wts mice: characterization of component cell populations.

Abstract

Three murine lymphomas of H-2a origin were investigated. Each of these lymphomas was derived in B10.H-2aH-4bp/Wts (2a4b) mice after a hyperimmunization protocol involving sheep red blood cells. Analysis of cell suspensions derived from the splenic tumors revealed a mixed lymphoid phenotype of the total cell population. Both the T-cell and B-cell populations remained after multiple passages of the tumors in syngeneic mice. A multiparameter approach combining immunologic and molecular genetic techniques was taken to determine the malignant cell population within these lymphomas. This analysis included depletion experiments utilizing histocompatible (B10.A X 21M)F1 mice to distinguish normal host-derived cells from the malignant tumor cells, fluorescence-activated cell sorting of the two cell populations followed by in vivo growth of the sorted cells, in vitro and in vivo cloning attempts, and molecular analysis of genomic DNA derived from the splenic tumors for clonal rearrangements of the immunoglobulin heavy-chain and T-cell receptor loci. Each of the three lymphomas was shown to be a malignant B-cell tumor that has an associated nonneoplastic T-cell component. The nature and functional significance of the numerous T-cells present in the B-cell lymphomas remain unknown and are being investigated.