Nephritogenic antibodies in MRL/lpr lupus mice: molecular characteristics in pathological and genetic aspects.

J. Itoh, S. Takahashi, M. Ono, T. Yamamoto, M. Nose, M. Kyogoku

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found that IgG3 production in this strain of mice has a critical role on the development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA levels of IgG3 correlated well with the severity of GN among the MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based on these results, we have successfully established five hybridoma clones which produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When they were injected to normal mice, four of the five clones generated cell-proliferative GN associated with the marked cellular infiltrates, while the remaining clone induced wire loop-like lesions. This result suggests that particular antibodies generated in MRL/lpr mice have a different pathogenic potency. The V-region sequence study of these nephritogenic antibodies revealed that the two types of the glomerular lesions were mediated by a different B cell precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by the expansion of clonally different B cells producing nephritogenic antibodies with a different pathogenic potency.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
Journalthe tohoku journal of experimental medicine
Volume173
Issue number1
DOIs
Publication statusPublished - 1994 May

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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