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Independent signals regulate development of primary and secondary follicle structure in spleen and mesenteric lymph node

1997; National Academy of Sciences; Volume: 94; Issue: 11 Linguagem: Inglês

10.1073/pnas.94.11.5739

1091-6490

Yang‐Xin Fu, Guangming Huang, Mitsuru Matsumoto, Hector Molina, David Chaplin,

T-cell and B-cell Immunology

Lymphotoxin-α-deficient (LT-α −/− ) mice manifest congenital absence of lymph nodes (LNs) and Peyer’s patches and disturbed spleen follicle 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 I-deficient (TNFR-I −/− ) mice show similar absence of FDC clusters and GCs but retain segregation of T and B cell zones. Rarely are mesenteric LNs found in LT-α −/− mice. These mesenteric LNs show segregation of T and B cell zones similar to wild-type mice. In contrast, mesenteric LNs in TNFR-I −/− mice manifest grossly disturbed organization of T and B cells. Both LT-α −/− and TNFR-I −/− mice lacked FDC clusters in LNs and spleen. Interestingly, although both LT-α −/− and TNFR-I −/− mice that had been immunized with sheep red blood cells failed to form GCs in the spleen, they both developed GC-like clusters of peanut agglutinin-positive (PNA + ) cells in their LNs. Furthermore, when lethally irradiated recombination activating gene (RAG)-1-deficient (RAG-1 −/− ) mice that had received spleen cells from LT-α −/− mice were immunized with sheep red blood cells, they failed to generate PNA + clusters in the reconstituted spleen but showed robust PNA + clusters in the reconstituted LNs. These data demonstrate that the signals that regulate the development of distinct T and B cell zones as well as the signals that regulate B cell activation to produce clusters of PNA + cells differ between the spleen and LNs.