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J. Exp. Med.,
Volume 189, Number 1, January 4, 1999 159-168
Receptor by Radioresistant
Stromal Cells and of Lymphotoxin
and Tumor Necrosis
Factor by B Cells
By



From the * Institute of Medical Microbiology, Immunology and Hygiene, Technical University of
Munich, D-81675 Munich, Germany; the The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT)
Institute for Genetics, University of Cologne,
D-50931 Cologne, Germany; § Serono Pharmaceutical Research Institute, Plan-les-Ouates,
CH-1228, Switzerland; and the
Engelhardt Institute of Molecular Biology and Belozersky Institute
of Physico-Chemical Biology, 117984 Moscow, Russia
, and LT
, as well as their receptors TNF receptor p55
(TNFRp55) and LT
R play essential roles in the development of GCs. To establish in which
cell types expression of LT
R, LT
, and TNF is required for GC formation, LT
R
/
,
LT
/
, TNF
/
, B cell-deficient (BCR
/
), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA+) clusters of centroblasts/centrocytes in association with follicular dendritic
cell (FDC) networks, were not detectable in LT
R
/
hosts after transfer of wild-type BM. In
contrast, the GC reaction was restored in LT
/
hosts reconstituted with either wild-type or
LT
R
/
BM. In BCR
/
recipients reconstituted with compound LT
/
/BCR
/
or
TNF
/
/BCR
/
BM grafts, PNA+ cell clusters formed in splenic follicles, but associated
FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks
depends on expression of LT
and TNF by B lymphocytes and LT
R by radioresistant stromal cells.
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