Independent signals regulate development of primary and secondary follicle structure in spleen and mesenteric lymph node.
Lymphotoxin-alpha-deficient (LT-alpha-/-) 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-alpha-/- 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-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 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-alpha-/- 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.
Fu
Y X
YX
Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Huang
G
G
Matsumoto
M
M
Molina
H
H
Chaplin
D D
DD
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018398:Homeodomain Proteins; D008198:Lymph Nodes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000276:immunology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology*; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018398:Homeodomain Proteins; D008233:Lymphotoxin-alpha; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C064658:RAG-1 protein