Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precursors into splenic follicles.
The development and function of secondary lymphoid tissue require signaling by tumor necrosis factor and lymphotoxins. Mice deficient in LTbetaR show defective organogenesis of lymph nodes and Peyer's patches and a severely disturbed splenic architecture. In contrast, TNF or p55TNF-R deficiency does not affect the organogenesis of peripheral lymphoid organs but interferes with the formation of B cell follicles and the appearance of FDC networks and germinal centers in all secondary lymphoid organs. Based on these differences, we have previously hypothesized that the role of TNF in lymphoid structure is distinct from that of LT and restricted in regulating cellular interactions that allow the differentiation and/or correct positioning of FDCs. In the present study we show that, in addition to the defects in follicular structure, TNF or p55TNF-R knockout mice exhibit defects in the formation of the macrophage populations and of the sinus lining cells of the splenic marginal zone. Interestingly, a large number of dendritic-shaped cells stained with FDC-specific markers and able to trap immune complexes are retained within the defective marginal zone of TNF and p55TNF-R knockout spleens. We conclude that the primary defect in the lymphoid phenotype of TNF or p55TNF-R knockout mice is the failure of FDC precursors to migrate through the disorganized marginal sinus and to home properly into the splenic follicular areas where they would promote the formation of B cell follicles and germinal centers.
Pasparakis
M
M
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, 115 21, Greece.
Kousteni
S
S
Peschon
J
J
Kollias
G
G
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D020566:Dendritic Cells, Follicular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha