PEYERS PATCH ORGANOGENESIS IS INTACT YET FORMATION OF B-LYMPHOCYTE FOLLICLES IS DEFECTIVE IN PERIPHERAL LYMPHOID ORGANS OF MICE DEFICIENT FOR TUMOR-NECROSIS-FACTOR AND ITS 55-KDA RECEPTOR

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymp hotoxin (LT) ligand and receptor system has recently revealed essentia l roles for these molecules in lymphoid tissue development and organiz ation. Lymphotoxin-alpha beta (LT alpha beta)/lymphotoxin-beta recepto r (LT beta-R) signaling is critical for the organogenesis of lymph nod es and Peyer's patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal z ones. Moreover, an essential role has been demonstrated for TNF/p55 tu mor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, an d germinal centers. In contrast to a previously described essential ro le for the p55TNF-R in Peyer's patch organogenesis, we show in this re port that Peyer's patches are present in both TNF and p55TNF-R knockou t mice, demonstrating that these molecules are not essential for the o rganogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer's patches. However, a lthough B cells are found to home normally within Peyer's patches and in the outer cortex area of lymph nodes, organized follicular structur es and follicular dendritic cell networks fail to form, These results show that in contrast to LT alpha beta signaling, TNF signaling throug h the p55TNF-R is not essential for lymphoid organogenesis but rather for interactions that determine the cellular and structural organizati on of B cell follicles in all secondary lymphoid tissues.