A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus

Owen T.M. Chan, Lynn G. Hannum, Ann M. Haberman, Michael P. Madaio, Mark J. Shlomchik

Research output: Contribution to journalArticle

551 Scopus citations

Abstract

The precise role of B cells in systemic autoimmunity is incompletely understood. Although B cells are necessary for expression of disease (Chan, O., and M.J. Shlomchik. 1998.J. Immunol. 160:51-59, and Shlomchik, M.J., M.P. Madaio, D. Ni, M. Trounstine, and D. Huszar. 1994. J. Exp. Med. 180:1295- 1306), it is unclear whether autoantibody production, antigen presentation, and/or other B cell functions are required for the complete pathologic phenotype. To address this issue, two experimental approaches were used. In the first, the individual contributions of circulating antibodies and B cells were analyzed using MRL/MpJ-Fas(lpr) (MRL/lpr) mice that expressed a mutant transgene encoding surface immunoglobulin (Ig), but which did not permit the secretion of circulating Ig. These mice developed nephritis, characterized by cellular infiltration within the kidney, indicating that B cells themselves, without soluble autoantibody production, exert a pathogenic role. The results indicate that, independent of serum autoantibody, functional B cells expressing surface Ig are essential for disease expression, either by serving as antigen-presenting cells for antigen-specific, autoreactive T cells, or by contributing directly to local inflammation.

Original languageEnglish (US)
Pages (from-to)1639-1647
Number of pages9
JournalJournal of Experimental Medicine
Volume189
Issue number10
DOIs
StatePublished - May 17 1999

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Keywords

  • Antigen presentation
  • Nephritis
  • T cell
  • Transgenic
  • Vasculitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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