ISSN:
1365-3083
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
The initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2ab of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1-derived IgG2ab monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (Kd) for soluble nuc particles was approximately 7 × 10−10 m. The mAbs bound more weakly to both H2A–H2B-DNA and H3–H4-DNA complexes, and in immunoblot they stained all four core histones. The mAbs detected a surface antigen on all cell lines examined, present on viable cells. When stripped of nuc , and in the presence of DNase I, their binding to cell lines improved. Heparin displaced the antigen from the cell surface. In vivo, the three mAbs stained B cells of several BALB/c mice clearly stronger than the isotype control; this differential staining was significantly reduced in FcγRIIB-deficient mice. The results indicate that the three mAbs recognize (a) planted antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to immune complexes that bind to FcγRIIB. Further experiments demonstrated that antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence, at least part of the extrinsic IgG2ab found on BXSB B cells may represent FcγRIIB-bound nuc-IgG2ab complexes.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.0300-9475.2004.01476.x
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