A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus

DOI PDF 被引用文献21件
  • Owen T.M. Chan
    From the *Section of Immunobiology and the ‡Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the §Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
  • Lynn G. Hannum
    From the *Section of Immunobiology and the ‡Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the §Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
  • Ann M. Haberman
    From the *Section of Immunobiology and the ‡Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the §Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
  • Michael P. Madaio
    From the *Section of Immunobiology and the ‡Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the §Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
  • Mark J. Shlomchik
    From the *Section of Immunobiology and the ‡Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the §Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

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<jats:p>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-Faslpr (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.</jats:p>

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