Follicular dendritic cell dysfunction and disorganization of lymphoid structures in MRL/lpr mice.
The follicular dendritic cell (FDC) in secondary lymphoid organs plays a key role in the function of the germinal center (GC) of the lymphoid follicle (LF) for regulation of the humoral immune response. MRL MpJ-lpr/lpr (MRL/lpr) mice, which have an abnormal humoral immune response, are a model for autoimmune disease. The present study was undertaken to investigate FDC dysfunction and LF disorganization in the spleen and lymph nodes of MRL/lpr mice. In 12-week-old MRL/lpr mice, antigen (Ag) trapping of FDC and half-life of trapped Ag on FDC was reduced. Although immunohistochemistry revealed well-developed FDC networks positive for complement receptors and having in vitro immune complex trapping in cryostat sections, Ag-trapping was not detected in 16-week-old MRL/lpr mice. Moreover a marked decrease in the number of GC and that of GC cell of residual GC in the MRL/lpr mice was observed by 12 weeks of age. Also reduced expression of intercellular adhesion molecule-1, FcgammaRII/III, and FDC-specific Ag (FDC-M1) on FDC was detected in 16-week-old MRL/lpr mice. The accumulation of double negative (CD4-CD8-) T cells, which is a characteristic feature of MRL/lpr mice, was observed around LF; however they did not infiltrate the LF and FDC network. In conclusion the loss of Ag-trapping on FDC and simultaneous disorganization of the lymphoid structure may be related closely to the immunologic abnormality observed in MRL/lpr mice.
Department of Pathology, School of Medicine, Tokyo Women's Medical University, Japan.
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Masuda
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Kasajima
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000473:pathology / Q000503:physiopathology*; D003713:Dendritic Cells / Q000502:physiology*; D000939:Epitopes; D005260:Female; D005629:Frozen Sections; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008208:Lymphatic System / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013154:Spleen / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D018799:Intercellular Adhesion Molecule-1