|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 188, Number 4, August 17, 1998 745-754
Knockout Mice
with Tumor Necrosis Factor-expressing Transgenes
Rectifies Defective Splenic Structure and Function
By
From the Department of Molecular Genetics, Hellenic Pasteur Institute, 115 21 Athens, Greece
Lymphotoxin (LT)
knockout mice, as well as double LT/tumor necrosis factor (TNF)
knockout mice, show a severe splenic disorganization with nonsegregating T/B cell zones and
complete absence of primary B cell follicles, follicular dendritic cell (FDC) networks, and germinal centers. In contrast, as shown previously and confirmed in this study, LT
-deficient
mice show much more conserved T/B cell areas and a reduced but preserved capacity to form
germinal centers and FDC networks. We show here that similar to the splenic phenotype of
LT-deficient mice, complementation of LT knockout mice with TNF-expressing transgenes leads to a p55 TNF receptor-dependent restoration of B/T cell zone segregation and a
partial preservation of primary B cell follicles, FDC networks, and germinal centers. Notably,
upon lipopolysaccharide challenge, LT knockout mice fail to produce physiological levels of
TNF both in peritoneal macrophage supernatants and in their serum, indicating a coinciding deficiency in TNF expression. These findings suggest that defective TNF expression contributes to the complex phenotype of the LT knockout mice, and uncover a predominant role
for TNF and its p55 TNF receptor in supporting, even in the absence of LT, the development and maintenance of splenic B cell follicles, FDC networks, and germinal centers.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
