The major goal of this research is to generate a library of closely related, transplantable lymphomas in a single inbred strain of mice. Specifically, we aim to accomplish the following: (1) to induce a large number (more than 50) of primary lymphoid tumors in B10.H-2aH-4bp/Wts(2a4b) mice by procedures involving intense antigenic stimulation. Many of these tumors will be B-cell lymphomas (vide infra) with a minority of T-cell and macrophage tumors. Most of these tumors will be transplantable in 2a4b mice and most will convert readily to an ascites form; (2) from the above primaries, to establish a series of transplantable tumors such that 50 independently derived B-cell lymphomas are included. Cell suspensions from primary and early transplant generations of all tumors will be stored under liquid nitrogen; (3) to characterize, with respect to a battery of cell surface differentiation markers, the cells of each tumor which becomes established in transplantation; (4) to prepare specific xenogeneic anti-idiotype sera against the surface immunoglobulin of each independently derived B-cell lymphoma; (5) to determine the extent of crossreactivity between the idiotypes of the surface immunoglobulins of the 50 independently derived B-cell lymphomas; and (6) to catalog, with respect to surface differentiation markers, those B-cell, T-cell, and macrophage tumors which become established in transplantation and to make such tumors, together with histocompatible mice for transplantation, available for study by other interested investigators. At the end of the second year of this project, tumor induction is complete; over 700 primary lymphomas are stored under liquid nitrogen. About 35 B-cell and 50 T-cell tumors are characterized. Extensive idiotype sharing exists among the B-cell lymphomas. Antigen binding specificity of the IgM of 14 B lymphomas has been identified. One of the tumors, CH12, whose surface Ig reacts with sheep erythrocytes, has been used to study the mechanisms by which B cells may be induced to differentiate. These studies have led to definition of the surface IgM and 1-E molecules as true receptors which transduce differentiative signals across the cell membrane and formulation of a minimal model of MHC-restricted, antigen-specific signaling of B cells. This project has been renewed. (Ml)
| Willoughby, P B; Jennette, J C; Haughton, G (1988) Analysis of a murine B cell lymphoma, CH44, with an associated non-neoplastic T cell population. I. Proliferation of normal T lymphocytes is induced by a secreted product of the malignant B cells. Am J Pathol 133:507-15 |
| Willoughby, P B; Haughton, G (1988) Mixed phenotype lymphomas of B10.H-2a-H-4bp/Wts mice: characterization of component cell populations. J Natl Cancer Inst 80:351-60 |
| Haughton, G; Arnold, L W; Bishop, G A et al. (1986) The CH series of murine B cell lymphomas: neoplastic analogues of Ly-1+ normal B cells. Immunol Rev 93:35-51 |
| Pennell, C A; Arnold, L W; Lutz, P M et al. (1985) Cross-reactive idiotypes and common antigen binding specificities expressed by a series of murine B-cell lymphomas: etiological implications. Proc Natl Acad Sci U S A 82:3799-803 |
