This is a proposal to continue our studies on the immunological mechanisms that regulate the growth and immunoglobulin expression in murine plasmacytoma cells. A major objective is to extend our previous findings on the molecular mechanisms by which suppressor T cells specific for the idiotypic antigens expressed on the IgA lambda2 TNP-specific protein (M315) inhibit the synthesis and secretion of M315 by the BALB/c plasmacytoma MOPC-315. Suppression of M315 synthesis is triggered by a VH315-specific suppressor T cell induced by immunization of BALB/c mice with M315 or VH315. This suppressor cell produces a product that inhibits the expression of lambda2 mRNA in MOPC-315 cells without influencing the expression of alpha mRNA or J chain mRNA, and without influencing the synthesis of other proteins in MOPC-315 cells. Suppression of lambda2 mRNA is accompanied by the coordinate suppression of the trans located aberrantly rearranged lambda1 gene in MOPC-315 cells. Experiments are designed to determine if the trans regulation: a) is at the level of transcription, and b) involves activation of an endogenous repressor of light chain gene expression. MOPC-315 hybridomas that express a second monoclonal immunoglobulin, and MOPC-315 cells that express light chain genes introduced by transfection will be used to establish whether the light chain regulation is specific for lambda or lambda plus kappa light chains. Comparable studies will be carried out to investigate the mechanism of suppression of M460 synthesis in the IgA kappa, TNP-specific MOPC-460 plasmacytoma. Experiments will be done to determine if suppression and enhancement of M315 secretion by TNP-antigen specific regulation also involves the control of light chain expression. A third major objective is to further investigate the mechanisms that mediate idiotype-specific tumor immunity against plasmacytoma cells. These studies will develop important new information about the basic mechanisms by which immunoregulatory T cells control immunoglobulin expression in B cells and may provide the basic knowledge necessary to develop idiotype-specific regulatory strategies for the control of malignant B cells in humans.
| Waldschmidt, T J; Conrad, D H; Lynch, R G (1988) The expression of B cell surface receptors. I. The ontogeny and distribution of the murine B cell IgE Fc receptor. J Immunol 140:2148-54 |
| Lynch, R G; Mathur, A; Waldschmidt, T J et al. (1988) Immunoglobulin (Fc) receptors on murine T- and B-lymphocytes: investigations using tumor models. Mol Immunol 25:1151-7 |
| Lynch, R G (1988) Immunology of lymphoid cancer: probing of tumours and tumours as probes. Ann Inst Pasteur Immunol 139:71-83 |
| Urnovitz, H B; Chang, Y; Scott, M et al. (1988) IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific. J Immunol 140:558-63 |
| Mathur, A; Lynch, R G; Kohler, G (1988) Expression, distribution and specificity of Fc receptors for IgM on murine B cells. J Immunol 141:1855-62 |
