| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology, University of Chicago, Chicago, IL 60637
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-/- mice was
transferred into irradiated LT-/- mice or
TNF-/- mice. Interestingly, the formation of both GC and
FDC clusters in B cell follicles was restored in such chimeric mice,
suggesting that TNF and LT from different cells could complement one
another. To identify the exact contributions of each subset to the
complementary effect of TNF and LT, different sources of T and B cells
from LT-/- mice or TNF-/- mice were used
for reconstitution. Our study demonstrates that either T or B
cell-derived TNF is sufficient to restore FDC/GC in the presence of
LT-expressing B cells. However, TNF itself is not required for GC
reactions if the FDC network is already intact. Thus, the development
and maintenance of these lymphoid structures depend on a delicate
interaction between TNF and LT from different subsets of
lymphocytes. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
TNF, LT, and LT
are structurally homologous cytokines, and their
genes are closely clustered within a few kilobases of the MHC. TNF is
produced by both hemopoietic and nonhemopoietic cells in homotrimeric
form (TNF-3). LT exists as either a soluble
homotrimer (LT3) or a membrane heterotrimer
with LT and is detected on activated lymphocytes. TNF binds to
TNFR-I and TNFR-II on both lymphoid and nonlymphoid cells, whereas
membrane LT1/2 binds to LTR on nonlymphoid cells (1, 12, 13). This raises the possibility of different types of cell-cell
interactions between the TNF- and LT-producing and -responding
cells.
Both TNF-/- mice and
LT-/- mice lack FDC network in primary B
cell follicles and fail to form GC after immunization (1, 9). The relative contributions of LT and TNF in the formation of
secondary lymphoid tissues are still controversial (1, 14, 15). LT/TNF double-deficient mice showed an almost identical
phenotype as LT-/- mice, suggesting the
impaired TNF production in LT-/- mice
(6, 14). LT-/- mice were
reported to have 50–65% reduction of TNF production compared to
wild-type (wt) mice (14, 16). Alexopoulou et al. proposed
that the suppressed expression of the TNF gene in the
LT-/- mice is due to nearby transcriptional
interference by a phosphoglycarate kinase-neo selection
cassette within the targeted LT locus. Remarkably, they showed that
transgenic TNF mice on an LT-/- background
had ectopic GC but weakly restored FDC network (14).
Furthermore, a recent study has shown that mice deficient in both TNF
and LT exhibit altered microarchitecture in the spleen, which is
more severe than that in LT-/- mice
(17). They proposed that reduced expression of TNF, rather
than LT, was responsible for the altered lymphoid follicles in
LT-/- mice (14). However,
recent evidence has also revealed that the action of LT in the
formation of GC and FDC clusters is independent from TNF. 1) Although
wt mice treated with LTR-Ig fail to form GC and FDC, this is not
seen in the mice treated with TNFR-Ig (8, 15). 2)
LTR-/- mice do not form FDC or GC. Deletion
of LT or TNF should have no impact on the expression of the LTR
gene, because the LTR gene is not clustered with the LT or TNF gene
(18, 19). Therefore, it is possible that both LT and TNF
play essential roles in the formation of GC and FDC in an independent
or complementary fashion.
To further study the relative contributions of LT and TNF to the
development of FDC and GC, we generated various forms of chimeric mice
from LT-/- mice or
TNF-/- mice. Our data showed that either T or B
cell-derived TNF in the context of B cell-derived LT is sufficient to
form FDC/GC. In addition, LT-deficient cells could make enough TNF for
reconstituted TNF-deficient mice to generate FDC/GC. Thus, our study
suggests that the development and maintenance of secondary lymphoid
structures depend on a delicate complementary effect between TNF and
LT from different subsets of lymphocytes.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
LT-/- mice (backcrossed to C57BL/6
mice for seven generations) and their wt littermates were bred under
specific pathogen-free conditions in the University of Chicago animal
facility (20). TCR-/-, B cell Ag
receptor (BCR)-/-, recombinase-activating
gene-1 (RAG-1)-/-,
TNFR-I-/-, TNF-/-, and
CD3
transgenic mice were purchased from The Jackson Laboratory (Bar
Harbor, ME). Animal care and use were in accordance with institutional
and National Institutes of Health guidelines.
Immunohistology
Spleens were harvested, embedded in OCT compound (Miles, Elkhart, IN), and frozen at -70°C. Frozen sections (6–10 µm thick) mounted on slides were fixed in cold acetone. Endogenous peroxidase was quenched with 0.2% H2O2 in methanol. After washing in PBS, the sections were stained by first incubating with FITC-conjugated anti-B220 (for B cells), biotinylated anti-complement receptor, CR1 (8C12, PharMingen, San Diego, CA), FDCM-1(2) (provided by Dr. Marie Kosco-Vilbois, Geneva, Switzerland), or biotinylated peanut agglutinin (PNA; Vector, Burlingame, CA), all at a 1/50–100 dilution for 1 h. After washing, HRP-conjugated rabbit anti-FITC (1/20; Dako, Glostrup, Denmark) and alkaline phosphatase-conjugated streptavidin (1/20; Vector) were incubated for 1 h. Color development was performed with an alkaline phosphatase reaction kit (Vector) and with 3,3'-diaminobenzidine (Sigma, St. Louis, MO). 8C12, an anti-CR1 Ab, binds to FDC clusters in both primary and secondary follicles better than B cells, and the staining using this Ab for FDC clusters is also brighter than that of FDC-M1, an anti-FDC Ab, in this condition. Therefore, 8C12 staining was presented throughout this study. We used both 8C12 and FDC-M-1 to visualize FDC clusters. We have not seen discordance between the two types of staining in B cell follicles in this study. Therefore, we used 8C12 to present FDC and FDC/GC to represent secondary B cell follicles in this study.
Enrichment for T and B cells
Nylon wool columns (Polysciences, Warrington, PA) were used to enrich spleen cell suspensions for T or B cells. Splenocytes were incubated on nylon wool columns with 10% FCS in DMEM for 1 h at 37°C. Nonadherent cells were eluted with 10% FCS in DMEM at 37°C. Enriched T cells in the fraction of nonadherent cells were further purified by panning on tissue culture dishes coated with goat anti-mouse Ig H/L chain (Southern Biotechnology Associates, Birmingham, AL), which yielded 75–85% T cells with <5% B cell contamination. The adherent cells on the nylon wool were eluted by cold PBS. Panning on tissue culture dishes coated with anti-Thy1.2 Ab reduced contamination of T cells to <5%.
Transfer of splenocytes, thymocytes, and bone marrow (BM) cells
Thymocyte (108) or splenocyte (5 x 107) suspensions were prepared from the mice as indicated and were injected i.v. into recipients that had been irradiated with 750 rad 3 h earlier. When indicated, 108 SRBC were injected i.v. soon after lymphocyte transfer. Recipients were irradiated with 1050 rad (200 rad/min) and were reconstituted with 5 x 106 donor BM cells in either a single preparation or a mixed preparation of 2.5 x 106 BM cells from each donor. Without reconstitution, no mouse would survive at such a high dose of radiation. Six to 8 wk (or as indicated) after BM transplantation (BMT), recipients were immunized i.p. with 108 SRBC. Sera or spleen were collected 10 days after immunization for ELISA or immunohistology, respectively.
Ag-specific IgG
Specific Abs were measured and analyzed as previously described (21). For measurement of anti-SRBC Abs, 96-well Falcon plates (Becton Dickinson, Lincoln Park, NJ) were coated with SRBC (150 µl of 0.1% SRBC in PBS/well). Diluted mouse serum was then added and incubated at 4°C for 1 h. Bound Abs were detected using 100 µl of 1/2000 diluted alkaline phosphatase-conjugated goat anti-mouse IgG-specific antiserum (Southern Biotechnology Associates), followed by addition of the alkaline phosphatase substrate p-nitrophenyl phosphate (Sigma) at 1 mg/ml. The mean OD at 405 nm from triplicate wells was compared with a standard curve of various titrated dilutions of a standard anti-SRBC immune serum. To calculate the relative units, we used linear regression analysis. The results are reported as the mean ± SEM.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Like LT-/- mice,
TNF-/- mice show no formation of FDC clusters
and GC after immunization. Unlike LTR-Ig, TNFR-Ig treatment failed
to block the formation of FDC clusters and GC in wt mice after
immunization with SRBC (8, 15). It is possible that the
action of TNF may not be blocked by TNFR-Ig or that prolonged blockage
of TNF activity is required for the prevention of FDC clustering.
Therefore, we performed BMT to evaluate the long term effect of
TNF-expressing cells on the formation of B cell follicles and FDC
network. BM cells from wt and TNF-/- mice were
reciprocally transferred into lethally irradiated wt or
TNF-/- mice. All the reconstituted mice were
also immunized with 108 SRBC 10 days before
harvest of the spleen. The spleens of reconstituted mice were collected
6, 10, 14, and 24 wk after BMT. Within the first 10 wk after BMT, the
ability to form FDC clusters and GC was unchanged in wt mice
reconstituted with TNF-deficient BM, but such ability gradually
decreased. By 24 wk, FDC clusters and GC were hardly detected in the wt
mice reconstituted with TNF-/- BM (Fig. 1
). The slow loss of FDC/GC after BMT may
explain why the 3-wk treatment of TNFR-Ig failed to block the formation
of FDC/GC in wt mice. In contrast, wt mice treated with LTR-Ig lost
their FDC clusters in <3 days, and wt mice reconstituted with
LT-/- BM more rapidly lost their ability to
form FDC within 2–3 wk after BMT (8, 21). It is likely
that TNF may act in different pathways than LT in both the development
and the maintenance of FDC clusters.
|
). It takes 3–4 wk to allow lymphocytes to mature and
repopulate peripheral lymphoid tissues after BMT and then another week
to respond to immunization. Therefore, the microenvironments for the
formation of B cell follicles and FDC clusters are not developmentally
fixed in TNF-/- mice and can be restored soon
(<2 wk) after TNF-expressing T and B cells mature and repopulate the
spleen. Our BMT data also suggest that TNF derived from hemopoietic
cells, but not from nonhemopoietic cells, determines the formation of
FDC/GC. Either TNF-expressing B cells or T cells could help TNF-/- mice restore the formation of FDC and GC
We and others have demonstrated that LT from B cells, but not that
from T cells, is essential for the formation of FDC (22, 23). To define which TNF-expressing cells were responsible for
delivering the essential signal in comparison with LT-expressing cells,
we analyzed the structures of spleen follicles from chimeric
TNF-/- mice that had been lethally irradiated
and reconstituted with mixed BM cells from
TNF-/- mice and either
BCR-/- or TCR-/- mice
(Fig. 2). Such a mixture of BM is used to
provide a selective source of TNF from either T or B cells as well as
retain all cellular components (T and B cells in particular) required
for GC. Six weeks after reconstitution, B cell follicles, FDC clusters
(determined by both 8C12 and FDC-M1), and GC were restored in
TNF-/- mice that had received the mixed BM
cells from TNF-/- mice and
TCR-/- mice (Fig. 2). This suggests that TNF
from T cells is not essential to complement TNF-deficient lymphocytes
to form secondary B cell follicles.
|
-/- mice,
TNF-/- mice that received both TNF-deficient
and BCR-deficient BM exhibited the formation of B cell follicles, FDC
clusters, and GC (Fig. 2 and Table I). It
appears that T cell-derived TNF may provide sufficient help to
TNF-deficient T/B cells to form FDC clusters. Interestingly, additional
TNF-expressing macrophages from RAG-1-deficient mice have no impact on
the restoration of either FDC or GC (Table I). Therefore, TNF from
either T or B cells is sufficient to assist TNF-deficient lymphocytes
to form FDC clusters and GC.
|
and TNF in the formation of GC
and FDC
Neither LT-deficient cells nor TNF-deficient cells alone can form
FDC clusters and GC, even when they are provided with a wt
microenvironment (15, 21) (Fig. 1). To test whether
LT- TNF+ cells and
TNF- LT+ cells together
could restore FDC clusters and GC, a mixture of BM cells from
TNF-/- and LT-/-
mice (1/1 ratio) was infused into lethally irradiated
TNF-/- mice. Six to 10 wk after BMT, the mice
were immunized with SRBC. Ten days following the immunization, the
spleens were collected, and immunohistochemistry was performed.
Interestingly, primary B cell follicles, FDC clusters (determined by
both 8C12 and FDC-M1), and GC (PNA clusters in B cell follicles) were
all restored, most likely accomplished by a complementary effect
between TNF from LT-deficient cells and LT from TNF-deficient cells
(Fig. 3A).
LT-/- mice have a more profound defect in
the spleen, generating no PNA+ cells or IgG in
response to SRBC, a strong T-dependent Ag (22, 23). To
investigate whether the complementary effect also occurred in an
LT-/- recipient, lethally irradiated
LT-/- recipients received a mixture of BM
cells from TNF-/- and
LT-/- mice. Although these reconstituted
mice still showed altered spleen architecture with ectopic central
arteriole and unsegregated T/B cell zones, these mice did restore FDC
clusters and form GC in response to T-dependent Ags (Fig. 3A). Therefore, the data suggest that a subset of
LT-deficient cells and another subset of TNF-deficient cells can
complement one another, providing enough TNF and LT signal to support
the formation of FDC and GC. Our data also demonstrate that cells from
LT-/- mice make enough TNF to support
TNF-deficient cells in the formation of FDC clusters and GC.
|
-/-
mice reconstituted with a mixture of BM cells from LT- and
TNF-deficient mice could restore IgG responses to T-dependent Ag, the
mice were immunized with SRBC 6 wk after BMT. The immunized mice showed
full recovery of their ability to produce Ag-specific IgG (Fig. 3B and Table I). These data indicate that the complementary
effect of LT and TNF derived from different subsets of cells is
sufficient to restore not only FDC clusters but also GC and IgG
response. Role of T cell- or B cell-derived TNF in the formation of FDC and GC
TNF can be produced by cells other than T and B cells. However,
TNF-deficient lymphocytes failed to form FDC and GC when they were
transferred into RAG-1-/- mice lacking T and B
cells (Fig. 4). Therefore,
lymphocyte-derived TNF is essential for the formation of FDC and GC. To
further address whether T cell-derived TNF is sufficient to support FDC
in TNF-/- mice, a mixture of thymocytes from wt
mice (a source of T cell-derived TNF) and splenocytes from
TNF-/- mice was transferred into
RAG-1-/- mice. FDC clusters formed within 10
days after the transfer (Fig. 4), suggesting that wt T cells complement
TNF-deficient B cells allowing the formation of FDC clusters.
Furthermore, the formed FDC clusters were functional because they
always support B cells to form GC in B cell follicles
(left panel in Fig. 4). The data suggest that B
cell-derived TNF is not absolutely required for the formation of FDC
and GC.
|
-/- mice) and LT+
TNF- splenocytes (from
TNF-/- mice) was transferred into
RAG-1-/- mice together with SRBC. Both GC and
FDC were then formed 10 days after transfer, although a smaller FDC
network and PNA+ clusters were detected compared
with the transfer of wt T cells (Fig. 4). Ten days after transfer, the
formation of PNA+ clusters was closely located
around the FDC network when wt T cells were provided, whereas about
half the PNA+ clusters were not colocalized with
the FDC network when LT+
TNF- splenocytes were provided (Fig. 4). The
data indicate that T cell-derived TNF is sufficient to assist
TNF-deficient lymphocytes in the formation of FDC and GC. In
contrast, LT-/- mice reconstituted with BM
cells from BCR-/- mice or with TNF-deficient T
cells failed to form any FDC clusters (22) (Table I).
Thus, our study demonstrates that LT from B cells, but not T cells,
is essential for the formation of FDC, whereas TNF from either T
cells or B cells can partially complement TNF-deficient splenocytes to
form both FDC and GC.
To study whether T cell-derived TNF is required for GC reactions in the
presence of intact FDC clusters, thymocytes (source of T cells) from
TNF-/- mice were transferred into
TCR-/- mice. Reconstituted mice were also
immunized with SRBC. TCR-/- mice were chosen as
recipients, because they have a well-established FDC network in the
primary B cell follicle, but cannot form secondary B cell follicles in
the absence of T cell help and SRBC (22). GCs were rapidly
formed around the FDC network in TCR-/- mice
reconstituted with T cells from either wt or
TNF-/- mice (Fig. 5). Consistently, TNF-deficient
lymphocytes were capable of forming GC in irradiated wt mice when the
clustering of FDC remained (data not shown). It appears that TNF is
required for the creation of the permissive environment to maintain GC
in B cell follicles. However, once the FDC network is established, TNF
may not be required for GC reactions.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
lack both FDC networks and PNA clusters inside B cell follicles
(1, 9), but it is unclear whether the effects of LT and
TNF can complement one another in the formation of FDC and GC. It has
not been well defined which cellular sources of LT and TNF are
essential for the formation of those structures. Here, we have clearly
demonstrated that 1) either T or B cells are able to supply TNF needed
for FDC and GC formation in the presence of B cell-associated LT; 2)
TNF is not essential for GC formation if FDC is present; and 3)
LT-/- cells make enough TNF for the
formation of FDC and GC. Due to the technical limitation of
immunohistology, the expression of LT/TNF protein by either T or B
cells in the FDC/GC area has not been demonstrated directly. We propose
that putative FDC precursors depend on signals from both TNFR and
LTR delivered by various lymphocytes for the differentiation,
migration, and maturation of FDC. Therefore, T and B cells coordinate
their effort to form GC around FDC via the complementary efforts of TNF
and LT.
Targeted disruption of genes that encode ligands and receptors in the
TNF/LT family has clearly established the important roles of these
molecules in the development and maintenance of secondary lymphoid
tissue (1, 14, 15). However, it was proposed that compound
defects in the production of both TNF and LT may occur in
LT-/- mice, and the resulting defect in TNF
caused by the nearby gene targeting may impair the formation of FDC/GC
(14). However, many other studies strongly support the
idea that an interaction between membrane LT and LTR is essential
for the formation of the T/B zone, FDC, and GC, independently from TNF
(8, 15, 16, 17, 18). In fact, wt mice treated with LTR-Ig, but
not TNFR-Ig, are prevented from developing GC and FDC (8, 15). If defective TNF expression in
LT-/- mice is the cause of the altered
lymphoid structure, then transferring cells from
LT-/- to TNF-/- mice
should not restore the formation of FDC clusters and GC in
TNF-/- mice. LT-deficient cells still make
sufficient TNF to assist TNF-deficient cells to form FDC and GC in B
cell follicles. Together with other evidence, it is likely that the
lack of FDC/GC in LT-/- mice is directly
attributed to the absence of LT, independent of the reduced expression
of TNF. The data also suggest that LT and TNF signals could be
delivered by different subsets of lymphocytes (Fig. 4).
In contrast to TNFR-/- mice, wt mice treated
with TNFR-Ig fail to block the formation of FDC/GC (8, 15). Our study indicates that prolonged deficiency of TNF, but
not short term deficiency, could lead to the loss of FDC and GC. It is
possible that signaling via TNFR is important for the early development
of the FDC network but is less important for the clustering of FDC and
their formation of GC. Prolonged blockage of TNF may be required for
the loss of established FDC due to the slow turnover rate of FDC and
the presence of LT. In contrast, LT may be more important for the
maintenance of FDC clustering. Blockage of LT will lead to the rapid
loss of FDC clustering. It was recently proposed that the lack of a
detectable FDC network in primary B cell follicles of
TNFR-/- mice may be due to the failure of FDC
precursors to migrate through the disorganized marginal zone to the
follicles (24). FDC-like cells are retained within the
defective marginal zone of TNF-/- or
TNFR-/- mice, but not in
LT-/- mice (24, 25). Therefore,
TNF and LT may act preferentially on different stages of FDC
differentiation.
Endres et al. recently found that the reconstitution of
BCR-/- mice with the mixture of
TNF-/- and BCR-/- BM
led to few FDC clusters (18). No PNA clusters were located
at B cell follicles, although some small clusters of PNA cells were
ectopically located around central arterioles in T cell areas. They
concluded that TNF-expressing B cells, but not T cells, are required
for the development of a mature splenic FDC network and GC. In
contrast, we have found that the reconstitution of
TNF-/- mice with the mixture of
TNF-/- and BCR-/- BM
led to the restored FDC clusters and GC in B cell follicles (Fig. 2).
The mechanisms for the apparent discrepancy are still under
investigation. It is possible that the BMT protocol, the treatment of
the recipient, the Ag used, and the housing conditions of the mice may
contribute to the underlining discrepancy.
There may be several explanations why LT from B cells, but not T cells,
is required for FDC clustering, whereas TNF from either T or B cells
can regulate FDC clustering: 1) the expression of LT may be more
limited to B cell follicles than that of TNF; 2) the time course of the
expression of TNF and LT may be different; 3) the soluble form of
TNF binds to TNFR, whereas only the membrane form of LT binds to
LTR; or 4) FDC clusters are surrounded by B cells inside B cell
follicles. Therefore, it may be difficult for cells other than B cells
to deliver membrane LT signal to FDC, because cell-cell contact is
required for the interaction between a membrane ligand and its
receptor. In contrast, both activated T and B cells near FDC could
deliver enough soluble TNF to FDC inside B cell follicles without
cell-cell contact.
Interestingly, transfer of either TNF- or LT-deficient splenocytes to
sublethally irradiated wt mice (750 rad) could generate GC when
radioresistant FDC still remained (15, 21). Soluble
TNFR-Ig administered in vivo failed to prevent GC (8, 15).
Furthermore, we have found that TNF-deficient T cells can help B cells
to form GC in TCR-/- recipients (Fig. 5).
Therefore, it appears that TNF is not essential for the formation of GC
inside B cell follicles once FDC is established, but TNF is necessary
for creating the permissive environment for B cell migration and GC
formation, probably by the development and/or maintenance of
FDC.
Both TNF and LT may not always be required for FDC maturation or
clustering. In some situations, a single signal from overexpression of
TNF or LT alone may be sufficient for lymphoid neogenesis. Expression
of TNF or LT by the transgenic approach can also lead to the generation
of some FDC networks and ectopic GC (14, 26). The
development of FDC and GC is closely associated with the development of
a pathological process, such as chronic inflammation or autoimmunity.
For example, patients with myasthenia gravis can manifest lymphoid
follicles and GC within the thymus. Similar follicles and GCs are found
with inflamed synovial tissues of patients with rheumatoid arthritis.
Lymphoid follicles, including FDC clusters, are developed in the islets
before the destruction of -cells in autoimmune diabetic mice. We
speculate that the formation of such follicles may greatly facilitate
Ag presentation and maintenance of the local immune response. It will
be of interest to study which cytokine(s) and which cells are involved
in the development and maintenance of such a lymphoid microenvironment
and their roles in chronic inflammation and autoimmune diseases.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Yang-Xin Fu, Department of Pathology, MC3083, Room J541, 5841 South Maryland, Chicago, IL 60637.
3 Abbreviations used in this paper: GC, germinal center; BM, bone marrow; BMT; BM transplantation; FDC, follicular dendritic cells; LT, lymphotoxin; wt, wild type; BCR, B cell Ag receptor; RAG-1, recombinase-activating gene-1; PNA, peanut agglutinin.
Received for publication March 17, 2000. Accepted for publication October 2, 2000.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
/ and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J. Exp. Med. 189:403.-deficient mice: a critical requirement for TNF in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med. 184:1397.-deficient mice. Proc. Natl. Acad. Sci. USA 94:9302. and revealed in lymphotoxin -deficient mice. Immunity 6:491.[Medline]
- complexes on the surface of mouse lymphocytes. J. Immunol. 159:3288.[Abstract]
knockout mice with tumor necrosis factor-expressing transgenes rectifies defective splenic structure and function. J. Exp. Med. 188:745. gene-targeted mice. J. Immunol. 163:1350. cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes. J. Immunol. 163:6575. receptor by radioresistant stromal cells and of lymphotoxin and tumor necrosis factor by B cells. J. Exp. Med. 189:159. receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9:59.[Medline]
(LT-) supports development of splenic follicular structure that is required for IgG responses. J. Exp. Med. 185:2111.This article has been cited by other articles:
|
|
 |
|
  J. Nilsson-Ohman, G. N. Fredrikson, L. M. Nilsson-Berglund, C. Gustavsson, E. Bengtsson, M.-L. Smith, C.-D. Agardh, E. Agardh, S. Jovinge, M. F. Gomez, et al. Tumor Necrosis Factor-{alpha} Does Not Mediate Diabetes-Induced Vascular Inflammation in Mice Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1465 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Beyer and M. Meyer-Hermann Mechanisms of organogenesis of primary lymphoid follicles Int. Immunol., April 1, 2008; 20(4): 615 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Y. Lee, W. Cho, J. Kim, C.-S. Park, and J. Choe Human Follicular Dendritic Cells Interact with T Cells via Expression and Regulation of Cyclooxygenases and Prostaglandin E and I Synthases J. Immunol., February 1, 2008; 180(3): 1390 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Anolik, R. Ravikumar, J. Barnard, T. Owen, A. Almudevar, E. C. B. Milner, C. H. Miller, P. O. Dutcher, J. A. Hadley, and I. Sanz Cutting Edge: Anti-Tumor Necrosis Factor Therapy in Rheumatoid Arthritis Inhibits Memory B Lymphocytes via Effects on Lymphoid Germinal Centers and Follicular Dendritic Cell Networks J. Immunol., January 15, 2008; 180(2): 688 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Duddy, M. Niino, F. Adatia, S. Hebert, M. Freedman, H. Atkins, H. J. Kim, and A. Bar-Or Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis J. Immunol., May 15, 2007; 178(10): 6092 - 6099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Thai, D. P. Calado, S. Casola, K. M. Ansel, C. Xiao, Y. Xue, A. Murphy, D. Frendewey, D. Valenzuela, J. L. Kutok, et al. Regulation of the Germinal Center Response by MicroRNA-155 Science, April 27, 2007; 316(5824): 604 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, Y. Liu, J. Wang, G. Ding, W. Zhang, G. Chen, M. Zhang, S. Zheng, and X. Cao Induction of Allospecific Tolerance by Immature Dendritic Cells Genetically Modified to Express Soluble TNF Receptor J. Immunol., August 15, 2006; 177(4): 2175 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, S. E. Blink, J. H. Chen, and Y.-X. Fu Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling J. Immunol., July 15, 2005; 175(2): 884 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Balogh, G. Horvath, and A. K. Szakal Immunoarchitecture of Distinct Reticular Fibroblastic Domains in the White Pulp of Mouse Spleen J. Histochem. Cytochem., October 1, 2004; 52(10): 1287 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Duddy, A. Alter, and A. Bar-Or Distinct Profiles of Human B Cell Effector Cytokines: A Role in Immune Regulation? J. Immunol., March 15, 2004; 172(6): 3422 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-M. Park, H.-Y. Park, and T. H. Lee Functional Effects of TNF-{alpha} on a Human Follicular Dendritic Cell Line: Persistent NF-{kappa}B Activation and Sensitization for Fas-Mediated Apoptosis J. Immunol., October 15, 2003; 171(8): 3955 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pihlgren, C. Tougne, P. Bozzotti, A. Fulurija, M. A. Duchosal, P.-H. Lambert, and C.-A. Siegrist Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens J. Immunol., March 15, 2003; 170(6): 2824 - 2832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Aucouturier and C. Carnaud The immune system and prion diseases: a relationship of complicity and blindness J. Leukoc. Biol., December 1, 2002; 72(6): 1075 - 1083. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
