Molecular analysis of spontaneous nephrotropic anti-laminin antibodies in an autoimmune MRL-Ipr/Ipr mouse

M. H. Foster, J. Sabbaga, S. R.P. Line, K. S. Thompson, K. J. Barrett, M. P. Madaio

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

To explore the genetic relationship between anti-laminin and anti-DNA autoantibodies (autoAb), V(H) gene and gene family expression were determined among autoAb derived from an individual 6-mo-old MRL-Ipr/Ipr mouse. Whereas 85% of the anti-DNA Ig were identified by one of two V(H) family probes, 7183 and V(H)J558, none of the anti-laminin antibodies (Ab) examined were recognized by these probes. Subsequent V region sequence analysis of three of the anti-laminin Ab revealed that they in fact utilized a J558 V(H) gene (V(H)50). Furthermore, FR2 and CDR2 oligonucleotide probes complementary to V(H)50 recognized multiple anti-laminin Ab by Northern blot analysis; the FR2 probe recognized two control anti-DNA Ab, but neither probe recognized anti- DNA Ab from the same mouse. Polymerase chain reaction amplification of MRL- Ipr/Ipr genomic liver DNA using primers generated from V(H)50 and V(k)50 sequences indicated that all three anti-laminin Ig have a single replacement mutation in both their V(H) and V(k) genes. Search of the nucleic acid databases revealed that both germline V(H) and V(k) genes are expressed unmutated by murine lupus anti-dsDNA autoAb, previously sequenced in other laboratories. Sequence comparisons suggest that differences in anti-DNA and anti-laminin reactivity may be dependent upon somatically generated differences in the CDR3 regions of the H and L chains. The results indicate that lupus anti-laminin Ab can arise from distinct B cell populations but express the same unmutated germline V region genes as lupus anti-dsDNA autoAb. They further raise the possibility that these distinct B cell populations may be activated and expanded either: independently, by distinct Ig receptor ligands such as the Ag, laminin and DNA; or simultaneously, by a common ligand such as an anti-Id recognizing a common V region epitope.

Original languageEnglish (US)
Pages (from-to)814-824
Number of pages11
JournalJournal of Immunology
Volume151
Issue number2
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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