Abstract

Antibodies related idiotypically to the pathogenic antibodies of SLE are produced in normal mice and humans. The production of these antibodies does not lead to the development of disease. The F1 (SNF1) progeny of the cross between a normal, nonautoimmune mouse, SWR and an autoimmune mouse, NZB, develops a severe, and accelerated glomerulonephritis. Immunoglobulin eluted from the renal lesions of SNF 1 mice are related idiotypically (IdLNF 1) related determinants can be produced by the normal SWR parent. The goal of this proposal is to identify any differences in the characteristics or expression of IdLNF 1+ antibodies in the SWR mouse, which distinguishes them from IdLNF 1+antibodies produced in the SNF 1 hybrid. Specifically, the precursor frequency of IdLNF 1+ b cells will be determined in the SWR and SNF 1 hybrid. IdLNF 1+ antibodies derived from unimmunized SWR mice by hybridoma technology will be characterized qualitatively and at the molecular level, to identify differences between these antibodies and IdLNF 1+ antibodies we have previously derived from SNF1 with disease. The kinetics of appearance and specificities of naturally occurring serum IdLNF 1+ antibodies and induced IdLNF 1 antibodies. Regulation of IdLNF 1+ immunoglobulin production by anti-idiotypic antibody and T cells in both strains of mice will be evaluated. The results of these studies will not only add to our understanding of immune regulation, but may help to identify specific mechanisms or defects which lead to the development of autoimmune glomerulonephritis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI026710-04
Application #
3454768
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1988-09-30
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Upstate Medical University
Department
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210

  Publications

Nyland, J F; Stoll, M L; Jiang, F et al. (2012) Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice. Lupus 21:1552-64
Stoll, Matthew L; Price, Karen D; Silvin, Christopher J et al. (2007) Immunization with peptides derived from the idiotypic region of lupus-associated autoantibodies delays the development of lupus nephritis in the (SWR x NZB)F1 murine model. J Autoimmun 29:30-7
Price, Karen; Knupp, Corey J; Tatum, Arthur H et al. (2002) Molecular identification of pathogenetic IdLNF+1 autoantibody idiotypes derived from the NZBxSWR F1 model for systemic lupus erythematosus. J Autoimmun 19:87-101
Uner, A H; Tatum, A H; Knupp, C J et al. (1998) Characteristics of auto anti-idiotypic antibodies reactive with antibodies expressing the pathogenic idiotype, IdLNF1, in the (NZB x SWR)F1 model for lupus nephritis and its parental strains. J Autoimmun 11:233-40
Dubnau, E; Soares, S; Huang, T J et al. (1996) Overproduction of mycobacterial ribosomal protein S13 induces catalase/peroxidase activity and hypersensitivity to isoniazid in Mycobacterium smegmatis. Gene 170:17-22
Knupp, C J; Uner, A H; Tatum, A H et al. (1995) IdLNF1-specific T cell clones accelerate the production of IdLNF1 + IgG and nephritis in SNF1 mice. J Autoimmun 8:367-80
Falcone, V; Bassey, E; Jacobs Jr, W et al. (1995) The immunogenicity of recombinant Mycobacterium smegmatis bearing BCG genes. Microbiology 141 ( Pt 5):1239-45
Uner, A H; Knupp, C J; Tatum, A H et al. (1994) Treatment with antibody reactive with the nephritogenic idiotype, IdLNF1, suppresses its production and leads to prolonged survival of (NZB x SWR)F1 mice. J Autoimmun 7:27-44
Pascopella, L; Collins, F M; Martin, J M et al. (1994) Use of in vivo complementation in Mycobacterium tuberculosis to identify a genomic fragment associated with virulence. Infect Immun 62:1313-9
Knupp, C J; Uner, A H; Korthas, C et al. (1993) Characterization of IdLNF1-specific T cell clones from the (NZB x SWR)F1 murine model for systemic lupus erythematosus. Clin Immunol Immunopathol 68:273-82

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