Expression of Anti-DNA Antibodies in Transgenic Mice

Scharff, Matthew D.

Abstract

We wish to examine the expression of an antibody that does not have significant binding for DNA in nonautoimmune and autoimmune mice and then to study the progeny of this antibody that arise through somatic mutation in both types of mice. We have selected an antibody that does not bind dsDNA but which in autoimmune NABWF1 mice acquires increased binding for dsDNA as it undergoes somatic mutation. We will examine the expression of the heavy and light chain of this antibody individually and together in NZW mice and examine the somatically mutated products of this antibody in this nonautoimmune strain. We will then mate NZW expressing both H and L to NZB and follow the expression and somatic mutation of the antibody in the autoimmune F1 animals.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program Projects (P01)
• Project #: 5P01AI033184-03
• Application #: 3747361
• Support Year: 3
• Fiscal Year: 1994

Institution

• Name: Albert Einstein College of Medicine
• DUNS #: 009095365
• City: Bronx
• State: NY
• Country: United States
• Zip Code: 10461

Publications

Valadon, P; Nussbaum, G; Oh, J et al. (1998) Aspects of antigen mimicry revealed by immunization with a peptide mimetic of Cryptococcus neoformans polysaccharide. J Immunol 161:1829-36

Nussbaum, G; Cleare, W; Casadevall, A et al. (1997) Epitope location in the Cryptococcus neoformans capsule is a determinant of antibody efficacy. J Exp Med 185:685-94

Gaynor, B; Putterman, C; Valadon, P et al. (1997) Peptide inhibition of glomerular deposition of an anti-DNA antibody. Proc Natl Acad Sci U S A 94:1955-60

Teller, K; Budhai, L; Zhang, M et al. (1996) HLA-DRB1 and DQB typing of Hispanic American patients with rheumatoid arthritis: the ""shared epitope"" hypothesis may not apply. J Rheumatol 23:1363-8

Valadon, P; Nussbaum, G; Boyd, L F et al. (1996) Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. J Mol Biol 261:11-22

Zhu, M; Green, N S; Rabinowitz, J L et al. (1996) Differential V region mutation of two transfected Ig genes and their interaction in cultured B cell lines. EMBO J 15:2738-47

Sakita, I; Horig, H; Sun, R et al. (1996) In vivo CTL immunity can be elicited by in vitro reconstituted MHC/peptide complex. J Immunol Methods 192:105-15

Zhang, M; Spey, D; Ackerman, S et al. (1996) Rheumatoid factor idiotypic and antigenic specificity is strongly influenced by the light chain VJ junction. J Immunol 156:3570-5

Valadon, P; Scharff, M D (1996) Enhancement of ELISAs for screening peptides in epitope phage display libraries. J Immunol Methods 197:171-9

Zhu, M; Rabinowitz, J L; Green, N S et al. (1995) A well-differentiated B-cell line is permissive for somatic mutation of a transfected immunoglobulin heavy-chain gene. Proc Natl Acad Sci U S A 92:2810-4