Lack of type 2 T cell-independent B cell responses and defect in isotype switching in TNF-lymphotoxin alpha-deficient mice.
TNF is implicated in in vitro Ig production, but its role in vivo is not clearly defined. Our previous studies had shown that TNF-LT alpha double-deficient mice have defective IgM and IgG primary Ab responses to the T cell-dependent (TD) Ag SRBC. We now extend these studies to secondary responses and to T cell-independent (TI) B cell responses. Injections of the TD Ag SRBC did not induce germinal center formation in the spleen of TNF-LT alpha-deficient mice. Associated with the morphologic defect, there was a defective IgG Ab response and a secondary hyper-IgM response to the TD Ag in TNF-LT alpha-deficient mice. The response to the TI Ag type 2 DNP-alanyl-glycyl-glycyl-Ficoll was essentially absent in TNF-LT alpha-deficient mice, while that to the TI Ag type 1 TNP-LPS was significantly reduced only for IgG2b isotype. Transplantation of bone marrow cells from wild-type mice into irradiated TNF-LT alpha-deficient mice restored the formation of splenic germinal centers and corrected the IgM and IgG responses to both TD and TI Ags. These data suggest that TNF and/or LT alpha signaling are critically required for germinal center formation and for the IgM and IgG responses to both TD and TI type 2 Ags.
Ryffel
B
B
Institute of Pathology, University of Basel, Switzerland.
Di Padova
F
F
Schreier
M H
MH
Le Hir
M
M
Eugster
H P
HP
Quesniaux
V F
VF
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004912:Erythrocytes / Q000276:immunology; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D018858:Germinal Center / Q000378:metabolism; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
C026941:2,4-dinitrophenyl-alanylglycylglycyl-ficoll; D000955:Antigens, T-Independent; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D005362:Ficoll