This research studies the mechanism of the isotype-specific suppression mediated by the T cells with Fc receptors found in mice with myeloma. We have previously shown that mice and patients with myeloma develop an increase in T cells with surface-membrane Fc receptors. Recently, we have found that the T cells with IgA-Fc receptors in IgA myeloma are isotype-specific suppresser cells. We, herein, propose to utllize normal immune response models to study the effects of T cells with IgA-Fc receptors (T-alpha cells) isolated from mice with IgA myeloma on: (1) the immunoglobulin isotype switch from mu to alpha; (2) the clonal expansion of IgA-committed B cells; (3) the differentiation of IgA committed B cells to secretory plasma cells; (4) the secretion of IgA plasma cells, and (5) their effects on other immunoregulatory T cells. We also intend to utilize MOPC-315 as an IgA myeloms-tumor model to study the effects of T-alpha cells on: (1) clonal growth of MOPC-315; (2) MOPC-315 tumor cell survival; (3) differentiation of MOPC-315; and (4) immunoglobulin production and secretion by MOPC-315. We also intend to iaolate and characterize any soluble-suppressor factors that are released by T-alpha cells found in mice with IgA myeloma cells. Finally, in order to confirm the generality of isotype-specific suppressor cell generation in myeloma, we will extend our studies of T-alpha cells and utilize similar models of normal immune responses and myeloma tumor models to study T-gamma cells in IgG myeloma and T-mu cells in IgM myeloma. The information generated from these studies is likely to: (1) contribute further to our understanding of the host response to myeloma that may ultimately lead to the development of specific immunotherapeutic strategies for the treatment of myeloma and related disorders; and (2) contribute to our understanding of the regulation of isotype expression during normal immune responses. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
5R23CA036403-02
Application #
3446521
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-01-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Roman, S; Moore, J S; Darby, C et al. (1988) Modulation of Ig gene expression by Ig binding factors. Suppression of alpha-H chain and lambda-2-L chain mRNA accumulation in MOPC-315 by IgA-binding factor. J Immunol 140:3622-30
Reed, J C; Alpers, J D; Scherle, P A et al. (1987) Proto-oncogene expression in cloned T lymphocytes: mitogens and growth factors induce different patterns of expression. Oncogene 1:223-8
Reed, J C; Prystowsky, M B; Kern, J A et al. (1987) Regulation of proto-oncogene expression during T lymphocyte activation and proliferation. Adv Exp Med Biol 213:249-62
Broome, H E; Reed, J C; Godillot, E P et al. (1987) Differential promoter utilization by the c-myc gene in mitogen- and interleukin-2-stimulated human lymphocytes. Mol Cell Biol 7:2988-93
Reed, J C; Alpers, J D; Nowell, P C et al. (1986) Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes. Proc Natl Acad Sci U S A 83:3982-6
Reed, J C; Abidi, A H; Alpers, J D et al. (1986) Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J Immunol 137:150-4
Reed, J C; Greene, W C; Hoover, R G et al. (1985) Monoclonal antibody OKT11A inhibits and recombinant interleukin 2 (IL 2) augments expression of IL 2 receptors at a pretranslational level. J Immunol 135:2478-82
Reed, J C; Sabath, D E; Hoover, R G et al. (1985) Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte. Mol Cell Biol 5:3361-8
Muller, S; Hoover, R G (1985) T cells with FC receptors in myeloma;suppression of growth and secretion of MOPC-315 by T alpha cells. J Immunol 134:644-7
Reed, J C; Nowell, P C; Hoover, R G (1985) Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation. Proc Natl Acad Sci U S A 82:4221-4