Molecular Analysis of the Human B Cells Repertoire

Capra, J Donald

Abstract

This study is directed towards testing the hypothesis that specific immunoglobulin variable, diversity and joining gene segments are involved in human systemic lupus erythematosus and other autoimmune diseases. It utilizes a novel mouse model of disease which includes human variable, diversity, joining and constant region genes in transgenic mice which have been backcrossed into autoimmune strains. Additionally, experiments are described to utilize homologous recombination (knockout) strains so that we can develop murine strains containing exclusively human antibody genes. The development of disease in such mice will provide the opportunity to analyze the utilization of specific variable, diversity and joining gene segments in these important models of human autoimmune disease. In addition to providing important information concerning the development of the human antibody repertoire, these studies may provide important insights into the role of circulating antibody in human systemic lupus erythematosus and hemolytic anemia.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program Projects (P01)
• Project #: 2P01AI031229-04
• Application #: 3747173
• Support Year: 4
• Fiscal Year: 1994

Institution

• Name: University of Texas Sw Medical Center Dallas
• City: Dallas
• State: TX
• Country: United States
• Zip Code: 75390

Publications

Nashi, Emil; Wang, YingHua; Diamond, Betty (2010) The role of B cells in lupus pathogenesis. Int J Biochem Cell Biol 42:543-50

Tao, Xuelian; Fan, Fred; Hoffmann, Victoria et al. (2008) Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F. Arthritis Rheum 58:1774-83

Dorner, T; Lipsky, P E (2005) Molecular basis of immunoglobulin variable region gene usage in systemic autoimmunity. Clin Exp Med 4:159-69

Ramanujam, Meera; Davidson, Anne (2004) The current status of targeting BAFF/BLyS for autoimmune diseases. Arthritis Res Ther 6:197-202

Dorner, Thomas; Lipsky, Peter E (2002) Abnormalities of B cell phenotype, immunoglobulin gene expression and the emergence of autoimmunity in Sjogren's syndrome. Arthritis Res 4:360-71

Dorner, Thomas; Hansen, Arne; Jacobi, Annett et al. (2002) Immunglobulin repertoire analysis provides new insights into the immunopathogenesis of Sjogren's syndrome. Autoimmun Rev 1:119-24

Girschick, Hermann J; Grammer, Amrie C; Nanki, Toshihiro et al. (2002) Expression of recombination activating genes 1 and 2 in peripheral B cells of patients with systemic lupus erythematosus. Arthritis Rheum 46:1255-63

Schiffer, L E; Hussain, N; Wang, X et al. (2002) Lowering anti-dsDNA antibodies--what's new? Lupus 11:885-94

Girschick, Hermann J; Lipsky, Peter E (2002) The kappa gene repertoire of human neonatal B cells. Mol Immunol 38:1113-27

Huang, Weiqing; Sinha, Jayashree; Newman, Jeffrey et al. (2002) The effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus. Arthritis Rheum 46:1554-62