INDEPENDENT SIGNALS REGULATE DEVELOPMENT OF PRIMARY AND SECONDARY FOLLICLE STRUCTURE IN SPLEEN AND MESENTERIC LYMPH-NODE

Lymphotoxin-alpha-deficient (LT-alpha(-/-)) mice manifest congenital a bsence of lymph nodes (LNs) and Peyer's patches and disturbed spleen f ollicle structure, The splenic white pulp areas show loss of discrete T and B lymphocyte zones, of follicular dendritic cell (FDC) clusters, and of germinal centers (GCs). Tumor necrosis factor receptor 1-defic ient (TNFR-I-/-) mice show similar absence of FDC clusters and GCs but retain segregation of T and B cell zones. Rarely are mesenteric LNs f ound in LT-alpha(-/-) mice, These mesenteric LNs show segregation of T and B cell zones similar to wild-type mice. In contrast, mesenteric L Ns in TNFR-I-/- mice manifest grossly disturbed organization of T and B cells, Both LT-alpha(-/-) and TNFR-I-/- mice lacked FDC clusters in LNs and spleen, Interestingly, although both LT-alpha(-/-) and TNFR-I- /- mice that had been immunized with sheep red blood cells failed to f orm GCs in the spleen, they both developed GC-like clusters of peanut agglutinin-positive (PNA(+)) cells in their LNs. Furthermore, when let hally irradiated recombination activating gene (RAG)-1-deficient (RAG- 1(-/-)) mice that had received spleen cells from LT-alpha(-/-) mice we re immunized with sheep red blood cells, they failed to generate PNA() clusters in the reconstituted spleen but showed robust PNA(+) cluste rs in the reconstituted LNs. These data demonstrate that the signals t hat regulate the development of distinct T and B cell zones as well as the signals that regulate B cell activation to produce clusters of PN A(+) cells differ between the spleen and LNs.