Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling

Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 1996-05, Vol.183 (5), p.2367-2372
Main Authors: Le Hir, M, Bluethmann, H, Kosco-Vilbois, M H, Müller, M, di Padova, F, Moore, M, Ryffel, B, Eugster, H P
Format: Article
Language:English
Subjects:
Animals
Antibody Formation
Cell Differentiation
Crosses, Genetic
Dendritic Cells - cytology
Dendritic Cells - immunology
Fluorescent Antibody Technique
Immunoglobulin Class Switching
Immunoglobulin G - blood
Immunoglobulin G - classification
Immunoglobulin M - blood
Lymphotoxin-alpha - genetics
Lymphotoxin-alpha - physiology
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Mutant Strains
Receptors, Tumor Necrosis Factor - physiology
Signal Transduction
Species Specificity
Spleen - cytology
Spleen - immunology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study, we extended these observations by determining which TNF receptor (TNFR) is involved in morphological and functional differentiation of the spleen. Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the LT beta-receptor pathway, displayed an abnormal microarchitecture, and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. In this strain, immunofluorescence revealed a lack of follicular dendritic cells (FDC) network, detected with FDC-M1 as well as anti-CR1, and a lack of germinal centers, detected with peanut agglutinin. In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.183.5.2367