Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice.
Lymphotoxin alpha (LT alpha)-deficient mice revealed critical roles for LT alpha in lymphoid organogenesis, but it is not clear whether LT alpha functions through an LT alpha homotrimer (LT alpha3) or LT alpha/beta heterotrimers. We generated LTbeta-deficient mice and found them to lack Peyer's patches, peripheral lymph nodes, splenic germinal centers, and follicular dendritic cells. Unlike LT alpha-deficient mice, LT beta-deficient mice had cervical and mesenteric lymph nodes. Furthermore, the mesenteric lymph nodes had germinal center-like regions, although these structures appeared to lack follicular dendritic cells. The absence of cervical and mesenteric lymph nodes in LT alpha-deficient mice, and yet their presence in LT beta-deficient mice and in mice deficient in tumor necrosis factor receptor types I and II, suggest that LT alpha3 may signal via an as yet unidentified receptor.
Koni
P A
PA
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sacca
R
R
Lawton
P
P
Browning
J L
JL
Ruddle
N H
NH
Flavell
R A
RA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000737:chemistry / Q000473:pathology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000196:embryology* / Q000276:immunology* / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000502:physiology*; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007136:Immunoglobulins; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha