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.