Loss of follicular dendritic cells in murine-acquired immunodeficiency syndrome.

BACKGROUND

The disease caused by HIV-1 leads to the destruction of follicular dendritic cells (FDC) and the follicular architecture in secondary lymphoid tissues. The murine acquired immunodeficiency syndrome (MAIDS, caused by LP-BM5) serves as an animal model for study of mechanisms involved in development of retrovirus-induced immunodeficiencies. The present study was undertaken to determine whether LP-BM5 infection leads to the destruction of murine FDC and the normal follicular architecture in secondary lymphoid tissues.

EXPERIMENTAL DESIGN

Mice were infected with LP-BM5, and the follicular architecture and FDC networks were assessed. The pathologic changes observed were correlated with FDC function.

RESULTS

Three weeks after infection, FDC networks were present, and they often appeared hyperplastic. However, by 1 month after infection, distorted lymphoid follicles were apparent, and the intensity of FDC labeling began to decline. FDC disappeared first in the spleen, and in hyperimmunized mice, FDC in draining lymph nodes disappeared before FDC in nondraining lymph nodes. By 4 months, the normal follicular localization of B cells was missing, and FDC were not detectable in most tissues. As the FDC and the normal lymphoid architecture degenerated, extrafollicular foci of immunoblasts and plasma cells appeared in areas typically reserved for T cells, and the Thy 1.2+ T cells were dispersed. Of interest, the total number of Ig-producing cells increased as the disease progressed; in contrast, the number of anti-human serum albumin-producing cells in mice immunized with human serum albumin before infection decreased.

CONCLUSIONS

These data indicate that, like HIV-1 infection, LP-BM5 infection leads to the loss of FDC and the normal follicular architecture. However, morphologic changes were not observed until after FDC had lost their normal ability to trap and retain Ag. These data indicate that retroviral infections may cause FDC dysfunctions long before FDC are destroyed.