Abstract
B cell hyperactivity, hypergammaglobulinemia, and autoantibody expression, the hallmarks of systemic lupus erythematosus, might be associated with structural abnormalities within the Ig heavy chain variable region (Igh-V) gene complex. The Igh-V loci from several lupus- prone mouse strains, their ancestors, and other nonautoimmune mice were therefore analyzed by restriction fragment length polymorphisms with DNA probes corresponding to seven VH gene families. These seven families comprise the majority of the known polymorphic murine VH gene repertoire, including some involved in autoantibody generation. Our study showed that the Igh-V loci from lupus and haplotype-matched nonlupus mice resulted in essentially identical restriction fragment patterns, a finding which suggests that the Igh-V gene complex does not carry a primary defect responsible for autoimmune disease.
Full Text
The Full Text of this article is available as a PDF (712.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bocchieri M. H., Cooke A., Smith J. B., Weigert M., Riblet R. J. Independent segregation of NZB immune abnormalities in NZB x C58 recombinant inbred mice. Eur J Immunol. 1982 Apr;12(4):349–354. doi: 10.1002/eji.1830120417. [DOI] [PubMed] [Google Scholar]
- Brodeur P. H., Riblet R. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol. 1984 Oct;14(10):922–930. doi: 10.1002/eji.1830141012. [DOI] [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Eilat D., Hochberg M., Pumphrey J., Rudikoff S. Monoclonal antibodies to DNA and RNA from NZB/NZW F1 mice: antigenic specificities and NH2 terminal amino acid sequences. J Immunol. 1984 Jul;133(1):489–494. [PubMed] [Google Scholar]
- Gavalchin J., Nicklas J. A., Eastcott J. W., Madaio M. P., Stollar B. D., Schwartz R. S., Datta S. K. Lupus prone (SWR x NZB)F1 mice produce potentially nephritogenic autoantibodies inherited from the normal SWR parent. J Immunol. 1985 Feb;134(2):885–894. [PubMed] [Google Scholar]
- Kofler R., Noonan D. J., Levy D. E., Wilson M. C., Møller N. P., Dixon F. J., Theofilopoulos A. N. Genetic elements used for a murine lupus anti-DNA autoantibody are closely related to those for antibodies to exogenous antigens. J Exp Med. 1985 Apr 1;161(4):805–815. doi: 10.1084/jem.161.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kronenberg M., Kraig E., Siu G., Kapp J. A., Kappler J., Marrack P., Pierce C. W., Hood L. Three T cell hybridomas do not contain detectable heavy chain variable gene transcripts. J Exp Med. 1983 Jul 1;158(1):210–227. doi: 10.1084/jem.158.1.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parsons M., Cazenave P. A., Herzenberg L. A. Igh-4D, a new allotype at the mouse IgG1 heavy chain locus. Immunogenetics. 1981;14(3-4):341–344. doi: 10.1007/BF00342202. [DOI] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
- Woods V. L., Jr, Scher I., Lieberman R., Paul W. E. IgD allotypic determinants. II. Determinants expressed on IgD of mice of the b, e, and o Igh-C haplotypes. J Immunol. 1980 Dec;125(6):2708–2712. [PubMed] [Google Scholar]