The aim of this proposal is to understand the structure and the molecular genetic origins of anti-DNA antibodies found in patients with SLE. I will study antibodies reactive with the monoclonal anti-idiotype F4 that recognizes a heavy chain determinant on cationic IgG anti-DNA antibodies from patients with SLE. I will examine the antigenic fine specificity of F4 reactive antibodies from SLE sera and EBV transformed B cell lines and correlate antigenic specificity with primary amino acid sequence of heavy and light chains. By cloning the VH genes of F4 reactive antibodies from human cell lines, I will determine how many gene families are used by SLE patients to encode F4 reactive antibodies. I hope to determine at the molecular level whether F4 reactive autoantibodies are encoded by genes found only in autoimmune individuals and whether they are encoded by germline genes or represent somatic events. I hope these studies will lead to an understanding of how autoantibodies arise and help suggest how normal regulation of these antibodies is achieved.
| Davidson, A; Schrohenloher, R E; Koopman, W J (1995) Molecular characterization of monoclonal IgM derived from human B cell lines expressing the 4C9 rheumatoid factor associated idiotype. Autoimmunity 20:171-83 |
| Davidson, A; Keiser, H D; del Puente, A et al. (1994) Expression of rheumatoid factor idiotypes 17.109, 6B6.6 and 4C9 in the sera of Pima Indians. Autoimmunity 18:251-8 |
| Youngblood, K; Fruchter, L; Ding, G et al. (1994) Rheumatoid factors from the peripheral blood of two patients with rheumatoid arthritis are genetically heterogeneous and somatically mutated. J Clin Invest 93:852-61 |
| Bonagura, V R; Artandi, S E; Davidson, A et al. (1993) Mapping studies reveal unique epitopes on IgG recognized by rheumatoid arthritis-derived monoclonal rheumatoid factors. J Immunol 151:3840-52 |
| Davidson, A; Lopez, J; Sun, D et al. (1992) A monoclonal anti-idiotype specific for human polyclonal IgM rheumatoid factor. J Immunol 148:3873-8 |
