Selective strain distribution pattern of a germline VH gene for a pathogenic anti-DNA autoantibody family

Shibnath Ghatak, Theresa L. O'keefe, Thereza Imanishi-kari, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Autoimmune NZB mice rarely develop nephritis, but the SNF, progeny of crosses between NZB and the normal SWR strain untformly develop severe lupus nephritis, indicating that the normal SWR strain makes a genetic contribution to the development of nephritis. The SNF, mice produce a select population of cationic IgG anti-DNA autoantibodies that share a recurrent crossreactive Idiotype called Id564 and these autoantibodies play a prominent role in the development of nephritls. These pathogenlc autoantibodles of SNF1, possess the lgCH allotype of the SWR, indicating their origin from the normal parent. The leader-V11, sequences of these ld564+ pathogenic anti-DNA autoantibodies are highly homologous and they are also related by 95% homology to a germline gene of normal C57BL/6 mice, called VH-23, that is a member of an anti-NP antibody gene family. Herein, we cloned the flanking and coding regions of the expressed VHDJH, genes of the anti-DNA mAb 564, the prototype member of the pathogenlc Id564 family. By restriction analysis and partial sequencing, we found that the VH564 gene is related but distinct in its 5' flanking region from all of the known anti-NP VH genes of C57BL/6 and BALB/c mlce. Hybridization with four probes complementary to different segments of the flanking and coding regions of the expressed VH564 gene indicated that the germline gene for VH564 is contained in an ̃5.2 kb EcoRl fragment of SWR genomic DNA. Moreover, high stringency hybridization with oligonucleotide probes complementary to unique CDR2 and 5' flanking sequences of the expressed VH564 gene revealed that the '̃5.2 kb' germline allele for VH564 that is possessed by the normal SWR parental strain is lacking In the NZB parental strain. C57BL/6 mice also lack this allele of the anti-DNA VH564 germline gene, although this strain possesses the highly homologous, anti-NP-related VH-23 germline gene. Thus germline VH genes for certain pathogenic autoantibodies may have a selective strain distribution pattern.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalInternational Immunology
Volume2
Issue number10
DOIs
StatePublished - Oct 1990

Keywords

  • Autoimmune disease
  • Lupus nephntis
  • Systemic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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