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 LT beta R sho w defective organogenesis of lymph nodes and Peyer's patches and a severely disturbed splenic architecture. In contrast, TNF or p55TNF-R deficiency do es not affect the organogenesis of peripheral lymphoid organs but interfere s with the formation of B cell follicles and the appearance of FDC networks and germinal centers in all secondary lymphoid organs. Based on these diff erences, we have previously hypothesized that the role of TNF in lymphoid s tructure is distinct from that of LT and restricted in regulating cellular interactions that allow the differentiation and/or correct positioning of F DCs. In the present study we show that, in addition to the defects in folli cular structure, TNF or p55TNF-R knockout mice exhibit defects in the forma tion of the macrophage populations and of the sinus lining cells of the spl enic marginal zone. Interestingly, a large number of dendritic-shaped cells stained with FDC-specific markers and able to trap immune complexes are re tained within the defective marginal zone of TNF and p55TNF-R knockout sple ens. We conclude that the primary defect in the lymphoid phenotype of TNF o r p55TNF-R knockout mice is the failure of FDC precursors to migrate throug h the disorganized marginal sinus and to home properly into the splenic fol licular areas where they would promote the formation of B cell follicles an d germinal centers. (C) 2000 Academic Press.