Murine interstitial nephritis. VI. Characterization of the B cell response in anti-tubular basement membrane disease

M. D. Clayman, L. Michaud, E. G. Neilson

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

In the present study we have examined the murine B cell response in anti-tubular basement membrane (α-TBM) disease. Whereas only certain strains of mice are susceptible to the development of interstitial lesions after immunization with heterologous renal tubular antigen, all strains make anti-tubular basement membrane antibodies (αTBM-Ab), and all express the 3M-1 kidney antigen which is the target of disease. The magnitude of the αTBM-Ab response in serum and renal eluates, measured by radioimmunoassay against crude tubular antigen or affinity-purified 3M-1, also mapped independently of susceptibility. The fine specificity of epitope binding was further analyzed using a rat monoclonal α3M-1 antibody to competitively inhibit the binding of renal eluate antibody to 3M-1. Maximum inhibition among nearly all tested strains ranged from 46 to 56% with no discernible difference between susceptible and nonsusceptible mice. Idiotypic representation of renal eluate αTBM-Ab was then evaluated by competitive inhibition using a polymorphic anti-idiotypic antisera. All mice examined possessed almost identical competitive inhibition patterns, indicating surprisingly similar idiotypic representation. Thus, in susceptible or nonsusceptible mice, neither the quantitative αTBM-Ab response, the epitopic fine specificity of that response, nor the idiotype of eluted αTBM-Ab serve as distinguishing markers for susceptibility to interstitial injury. Finally, passive transfer experiments with high-titered (greater than 1:10,000) αTBM-Ab from SJL mice were performed to test the hypothesis that αTBM-Ab alone may be sufficient for the induction of αTBM disease. Whereas this antiserum was capable of causing typical, severe αTBM disease in naive susceptible SJL mice, this treatment in allotype-identical, nonsusceptible B10.S(8R) mice was completely without effect. These data demonstrate, in conclusion, that, in the absence of appropriate susceptibility genes, αTBM-Ab are incapable of causing αTBM disease. The findings support previous observations that the ability of passively transferred αTBM-Ab to initiate interstitial injury is dependent on the host also expressing other susceptibility genes which promote the cooperative engagement of the cell-mediated immune response.

Original languageEnglish (US)
Pages (from-to)2242-2249
Number of pages8
JournalJournal of Immunology
Volume139
Issue number7
StatePublished - 1987

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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