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RI1
*
Department of Pathology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215; and
Department of Dermatology, Johns Hopkins Hospital, Baltimore, MD 21205
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResults and DiscussionReferences |
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RI network plays a central role in allergic
inflammation. IgE levels control cell surface levels of FcRI and, in
turn, FcRI levels modulate the intensity of effector responses.
Treatment of allergic patients with anti-IgE Abs has been shown to
induce a decrease in FcRI expression on basophils and a decrease in
Ag-triggered histamine release. However, the mechanisms underlying
IgE-mediated regulation of FcRI expression remain unclear. Here, we
designed an in vitro model system to establish the minimal cellular
requirements for regulation of FcRI by IgE. Using this system, we
demonstrate that transcriptional regulation, hemopoietic-specific
factors, and signaling are not required for IgE-mediated increases in
FcRI expression. IgE binding to the 
-chain is the minimal
requirement for the induction of FcRI up-regulation. The rate of
up-regulation is independent of the baseline level of expression. The
mechanism of this up-regulation is the result of a combination of three
factors: 1) stabilization of the receptor at the cell surface, which
prevents receptor internalization and degradation; 2) use of a
preformed pool of receptor comprising recycled and recently synthesized
receptors; and 3) continued basal level of protein synthesis. It is
possible that in vivo additional factors contribute to modulate the
basic regulatory mechanism described here. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
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RI complex forms a high affinity cell surface receptor for IgE
that is expressed in the tetrameric form (
2) on mast cells and
basophils and in the trimeric form (2) on eosinophils
(1, 2, 3) and APCs (4, 5, 6, 7). The -chain binds
IgE, and the -chain transduces signals (8). The
-chain is an amplifier of signal strength (9, 10) and
enhances the expression of unoccupied receptor at the cell surface
(11). Ligation of the receptor by IgE and multivalent Ag
results in the activation of multiple signaling pathways leading to
diverse effector responses.
FcRI is variably expressed on the cell surface. Long ago, before
FcRI had been characterized, the IgE binding capacity of human
basophils was shown to correlate with serum IgE concentrations
(12, 13). A number of studies have since confirmed that
IgE levels in vitro and in vivo regulate the cell surface expression of
FcRI (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25). Clinical trials treating allergic
patients with humanized Ab to IgE show recipients to exhibit decreased
levels of serum IgE with a concomitant decrease in surface expression
of FcRI on basophils (26, 27). More importantly, these
changes result in decreased histamine release in response to antigenic
challenge (26, 27), emphasizing the functional importance
of FcRI regulation by IgE. However, much is unknown about the
mechanisms that control this process. One study has shown the process
of up-regulation to be insensitive to cycloheximide, suggesting that
regulation does not involve protein synthesis (14). This
study proposed that inhibition of degradation of surface FcRI by IgE
could contribute to IgE-mediated up-regulation. However, the possible
contribution of other mechanisms such as recycling, was not
investigated. Later studies by Galli’s group (17) in
collaboration with us suggested a more complex situation: an early
cycloheximide-insensitive phase followed by a later
cycloheximide-sensitive phase, implying a requirement for protein
synthesis in the process. However, these studies do not differentiate
between a requirement for basal levels of protein synthesis vs a
requirement for increased protein synthesis. In addition, the
possibility of IgE-mediated variations in transcription, translation,
or message stability has not been investigated, and the relative
contribution from the proposed inhibition of degradation remains
unclear. Finally, a known amplifier of unoccupied receptor expression
is the -chain (11). However, its role in up-regulating
the expression of FcRI has not been studied.
To dissect the process of IgE-mediated regulation of FcRI, we have
created an in vitro cellular system that has allowed us to determine
the minimal cellular requirements necessary for IgE-mediated regulation
of FcRI. We have found that the minimum requirement to induce
up-regulation is binding of IgE to FcRI and that the mechanism of
this up-regulation involves receptor stabilization at the membrane,
recruitment of a preformed pool of receptors (recycled and recently
synthesized), and continued basal synthesis of receptors.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
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RI surface expression
U937 and NIH3T3 transfected cell lines were generated and
maintained as described previously (9). Experiments were
conducted in 96-well plates in triplicate at a density of 0.5 x
106 cells/ml. Chimeric human IgE (Serotec,
Oxford, U.K.), human myeloma IgE (BioDesign International, Saco, ME),
cycloheximide (1 µg/ml), or brefeldin A
(BFA3; 5 µg/ml;
Sigma, St. Louis, MO) were added at the initiation of culture for the
indicated times. For assessment of the cell surface levels of FcRI,
cells were incubated in saturating concentrations of human IgE followed
by FITC-conjugated goat anti-human IgE (BioSource International,
Camarillo, CA). Cells were analyzed by flow cytometry with FACScan
software (BD Biosciences, Franklin Lakes, NJ). Nonviable cells were
excluded by the addition of propidium iodide.
Immunoprecipitation and Western blotting
Cells were lysed as described previously (9). In
some experiments, lysates were treated with
endo--N-acetylglucosamidase (Endo H; New England Biolabs,
Beverly, MA; Ref. 28). For assessment of cell surface
FcRI, cell surface receptors were saturated with human IgE before
lysis and immunoprecipitated with mouse anti-human IgE (BD
PharMingen, San Diego, CA) coupled to protein G-Sepharose (Amersham
Pharmacia Biotech, Piscataway, NJ) in serial immunoprecipitations to
remove all surface receptors. Intracellular FcRI was
immunoprecipitated using monoclonal anti-human Ab, 15-1
(4), coupled to protein G-Sepharose. Samples were resolved
on 10% (for -chain) or 12.5% (for - and -chains) SDS
polyacrylamide gel in nonreducing conditions, transferred to
polyvinylidene fluoride membrane, and blotted with rabbit anti-human
Ab, 997 (28), anti-human Ab, 961
(11), or anti- Ab, 934 (29).
Immunoreactive proteins were visualized with alkaline phosphatase
coupled mouse anti-rabbit Ig, followed by enhanced
chemifluorescence (Amersham), and quantitated with the Storm scanner
(Molecular Dynamics, Sunnyvale, CA).
Northern blotting
Total cellular RNA was extracted using RNAzol B (Tel-Test;
Friendswood, TX). RNA was electrophoresed on 1% agarose gel and then
transferred to a nylon membrane. The membranes then were hybridized
with 32P-labeled cDNA probes for human , ,
and (30, 31, 32) as well as GAPDH as a positive control.
Probe binding was measured with a Storm scanner and quantitated with
ImageQuant software (Molecular Dynamics).
Statistical analysis
Numerical results are expressed as mean ± SD. Results were evaluated by ANOVA, which allows overall comparisons between a set of experimental data and a set of control data, for example, a time course. In some experiments, a Student’s paired t test was used to compare experimental data and control data at the same time point (pair) in the time course.
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Results and Discussion |
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TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
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RI expression does not require
transcriptional regulation or hemopoietic-specific factors
We reasoned that IgE-mediated FcRI up-regulation could be
mediated through the following mechanisms: an increase in
transcription, translation, or stability of the transcripts, improved
intracellular processing, or increased stability at the plasma membrane
of the FcRI subunits. Some of these mechanisms could require
cell-type-specific elements to operate. Our approach was to determine
the minimal requirements for FcRI up-regulation by using a
reconstitution system in which some of these potential factors could
not operate. In this system, reconstitution is achieved by introducing
(by transfection or infection) the cDNA for the molecule to be studied
in a cell line that does not express it spontaneously. This is a
general methodology that we have used successfully to dissect the
signaling machinery of FcRI (33, 34) and that of the
inhibitory receptor FcRIIb1 (35). We have also used it
to demonstrate the signal amplification and receptor expression
amplification functions of the -chain (9, 11). In
addition, we have validated this strategy by demonstrating that results
obtained with this in vitro system parallel results obtained in vivo
with animal models of allergic reactions (9, 10). Here we
have expressed FcRI in two different cell lines (see below) by
transfecting the cDNAs for the human -, -, and -chains. To
eliminate any requirement for increased transcription in IgE-mediated
FcRI up-regulation, we chose a viral promoter to drive expression of
the receptor subunits in the transfected cells. Such viral promoters
are stronger than eukaryotic promoters and are unlikely to be regulated
by eukaryotic factors. Their use ensured that transcription of the
FcRI subunits would be high and unaffected by IgE treatment. In
addition, to eliminate the contribution of mast cell-specific factors,
we generated these transfectants in the monocytoid cell line U937.
Cells transfected with the human , , and cDNAs or
untransfected cells were cultured in the presence of saturating
concentrations of monomeric IgE or vehicle and assessed for cell
surface expression of FcRI by flow cytometry. Fig. 1
A shows the ratio of FcRI
expression after incubation with IgE over FcRI expression after
incubation with vehicle as a function of time. IgE treatment
up-regulated FcRI expression, whereas it had no effect on
untransfected cells (p < E-4 vs IgE-treated
untransfected U937 and vs vehicle-treated transfectants). Note that in
the rat basophilic leukemia cell line RBL, which spontaneously
expresses FcRI, IgE-mediated up-regulation was comparable to that
observed with transfected FcRI (Fig. 1A). Because, in the
transfection system that we used here, expression was driven by a
nonregulated viral promoter, these studies demonstrate that
IgE-mediated up-regulation does not require increased transcription. In
addition, the ability to up-regulate FcRI in a non-FcRI
expressing, monocytoid line demonstrates that IgE-mediated
up-regulation does not require factors specific to mast cells or
basophils.
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, , and cDNAs. Here, too, IgE induced up-regulation of
FcRI expression (p < E-4 vs IgE-treated
untransfected NIH3T3 and vs vehicle-treated transfectants; Fig. 1
B). These experiments demonstrate that IgE-mediated
regulation does not require hemopoietic specific factors.
The -chain does not amplify IgE-mediated FcRI up-regulation
In humans, the -chain is not required for cell surface
expression, and an alternative trimeric (2) form exists. Although
not required for expression, the human -chain amplifies empty
receptor expression. By associating with FcRI early in the
endoplasmic reticulum, the -chain enhances processing of , and
trafficking of unoccupied receptor to the cell surface
(11). In addition, the -chain may enhance the stability
of the receptor, as suggested by increased resistance of 2
receptors to dissociation in the presence of detergent
(11). Because the -chain favors receptor trafficking to
the plasma membrane, it was possible that cells expressing the trimeric
form of FcRI would be less capable of increasing cell surface
expression of FcRI in response to IgE than 2 receptors. A
correlation has been shown between serum IgE levels and surface
expression of FcRI on blood cells expressing the trimeric receptor,
such as monocytes (6), suggesting that cells expressing
the trimeric receptor are indeed capable of up-regulating FcRI.
However, whether the -chain would amplify IgE-mediated up-regulation
has not been investigated. To examine the capacity of 2 receptors
to up-regulate in response to IgE, we stably transfected U937 with the
human - and -chain cDNAs alone and measured FcRI expression in
these 2 transfectants in response to IgE. Our data showed that
2 receptors were up-regulated as efficiently as 2
receptors and might be even more sensitive to IgE-mediated
up-regulation than 2 receptors, although further investigation
would be needed to confirm this observation (Fig. 1C). Thus,
we conclude that the -chain does not amplify IgE-mediated FcRI
up-regulation.
The rate of IgE-mediated FcRI up-regulation is independent of
the baseline level of FcRI expression
FcRI expression levels vary substantially among our transfected
cells with the mean fluorescence intensity (MFI) varying from 27 to 350
in U937 transfectants. To assess how the basal level of FcRI
expression influences IgE-mediated up-regulation, we plotted FcRI
expression after 24H of IgE treatment as a function of FcRI
expression after 24H of vehicle treatment for all the U937 clones
(n = 14) used in this study. Because the plot could be
fit to a straight line, it shows that FcRI up-regulation is directly
proportional to the basal level of FcRI expression (Fig. 2; slope = 2.912; r
= 0.932). This experiment demonstrates that the rate of FcRI
up-regulation by IgE is independent of the basal level of FcRI
expression in this reconstitution system.
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The signaling pathway of FcRI that results in degranulation and
liberation of allergic mediators is initiated by phosphorylation of the
- and -chains, which results in the generation of calcium flux
(reviewed in Refs. 8, 36 , and 37).
Aggregation of FcRI expressed in NIH3T3 cells results in only
minimal receptor phosphorylation and does not induce calcium
mobilization due to the lack of the hemopoietic-specific signaling
apparatus involved in FcRI signal transduction (33).
This inability to signal combined with the ability to up-regulate in
response to IgE in NIH3T3 transfectants (Fig. 1B) suggests
that classical signaling (i.e., involving activation of the Src family
kinase lyn) is not required for IgE-mediated up-regulation of FcRI.
To confirm that abrogation of the classical signaling pathway did not
prevent IgE-mediated up-regulation, we assessed FcRI transfectants
made with a tyrosine-mutated form of FcR instead of wild-type .
Mutation of the tyrosine residues in the immunoreceptor tyrosine
activation motif in the -chain renders it incapable of signaling
(38, 39, 40, 41). When these cells were cultured in the presence
of IgE, they showed increases in surface expression of FcRI (Fig. 3), demonstrating that classical
signaling is not required for up-regulation of FcRI by IgE.
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RI is capable of another type of signaling that has yet to be
described and that could be responsible for IgE-mediated up-regulation
by increasing transcription, message stability, or protein synthesis.
To evaluate this possibility, we examined total RNA and intracellular
protein levels for the -, -, and -chains in cells during
IgE-mediated up-regulation. U937 cells transfected with FcRI were
cultured in the presence of IgE or vehicle. At various time points,
cell surface expression was measured by flow cytometric analysis and by
immunoprecipitation of surface receptors. These levels were correlated
to the levels of intracellular proteins detected by immunoprecipitation
and to message levels detected by northern blot (Fig. 4). IgE treatment induced an increase in
surface , as assessed by immunoprecipitation (Fig. 4C),
which correlated with the increase detected by flow cytometry (Fig. 4A) for both the tetrameric and trimeric receptor.
Intracellular FcRI , , and revealed no increase over the
8-h time period in response to IgE (Fig. 4D and data not
shown). Northern blot showed no increase in message for (Fig. 4B), and (data not shown) at 4 or 8 h. These
studies demonstrate that surface levels of FcRI can be increased
without increasing the rate of transcription or translation and without
increasing message stability.
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Recent studies have shown that IgE-mediated FcRI up-regulation
is sensitive to cycloheximide, reflecting a requirement for protein
synthesis (17). However, it has not been established
whether this sensitivity reflects a requirement for an increase in
protein synthesis or for the maintenance of the basal level of
synthesis. Our results showing up-regulation in the absence of
increased transcription suggest that the requirement for protein
synthesis would be for maintenance of basal levels of protein synthesis
rather than for increased protein synthesis. In addition, other studies
have attributed the effect of IgE to inhibition of receptor degradation
(14, 15, 43). In view of our results showing up-regulation
in the absence of increased transcription and of classical signaling,
the roles of receptor synthesis and receptor degradation were
re-examined.
Studies of other cell surface receptors have examined the effects of cycloheximide and BFA to estimate the relative impact of synthesis and recycling on receptor expression. Whereas cycloheximide inhibits translation, BFA prevents anterograde movement of newly synthesized protein from the endoplasmic reticulum to the Golgi (44, 45). It also causes early endosomes to fuse with the trans-Golgi membrane and inhibits receptor recycling. Therefore, comparison of the effect of cycloheximide and that of BFA on receptor expression allows one to determine the relative contribution of synthesis and recycling to receptor expression at the plasma membrane. Expression of receptors that are long-lived and exhibit a high degree of recycling is sensitive to BFA and much less to cycloheximide. Expression of receptors that recycle very little and do not depend on the availability of intracellular pools but require protein synthesis is equally sensitive to cycloheximide and BFA. And expression of receptors that rely on protein synthesis and intracellular pools is more sensitive to BFA than cycloheximide (46).
We first investigated the effect of cycloheximide and BFA on FcRI
over time in the absence of IgE. U937 cells transfected with the
tetrameric receptor were cultured in the absence of IgE with or without
cycloheximide or BFA and harvested at various time points (Fig. 5A). FcRI is expressed as
the ratio of MFI of treated samples to MFI of untreated samples at the
same time point. This study shows that receptor expression is sensitive
both to cycloheximide (p < E-4) and to BFA
(p < E-4). In addition, sensitivity to BFA is
1.5-fold that to cycloheximide (p <
5.5E-3), an indication that receptor expression at steady state depends
not only on protein synthesis but also on receptor recycling and the
availability of an intracellular pool.
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B). FcRI is expressed as the
ratio of MFI of IgE-treated samples to MFI of vehicle-treated samples
at the same time point. Cells treated with IgE and cycloheximide
increased their cell surface expression of FcRI for the first 4
h, but not after (p < E-4 vs vehicle treated).
However, the IgE-mediated increase in FcRI expression in the
presence of cycloheximide is less than the increase in the absence of
cycloheximide (p < 5E-4 vs IgE-treated). This
experiment demonstrates the existence of a pool of preformed receptors
that proceed to the plasma membrane, bind IgE, and contribute to
FcRI up-regulation even in the presence of cycloheximide. Once this
pool is exhausted (after 4 h) FcRI up-regulation cannot be
maintained in the presence of cycloheximide, demonstrating the complete
dependence of FcRI up-regulation on basal receptor synthesis once
the pool of preformed receptors is exhausted. In contrast, BFA
inhibited IgE-mediated up-regulation completely
(p < E-4 vs IgE treated, analyzed by ANOVA).
Inhibition also is immediate, as it is present already at 2 h
(p < 3E-2, analyzed by t test) and
it is maintained up to 8 h (p < 3E-2 at 4
and 6 h, p < 3E-3 at 8 h; analyzed by
t test). Thus, the effect of BFA on IgE-mediated
up-regulation is greater than that of cycloheximide
(p < 1E-2), suggesting that, in addition to
protein synthesis, use of a preformed intracellular pool and recycling
also are involved in the IgE-mediated up-regulation. Together with our
other data (Fig. 4) that show no increase in protein synthesis during
the IgE-mediated up-regulation process, these data demonstrate that in
this reconstituted system, maintenance of the basal level of synthesis,
use of an intracellular pool and recycling are sufficient to assure
IgE-mediated up-regulation. IgE acts by stabilizing receptors at the plasma membrane
We reasoned that, under the conditions of basal level protein synthesis, once the preformed pool of receptor is depleted, the only way to increase surface expression of receptor is to decrease surface receptor internalization and degradation.
By definition, at steady state, receptor accumulation on the cell
surface (from synthesis and recycling) is equal to receptor
disappearance from the cell surface (including degradation and
recycling). As indicated above, BFA blocks receptor accumulation and
recycling and therefore is ideal to reveal degradation rates (Fig. 5A). IgE-mediated up-regulation could be attributable to
stabilization of the receptors at the plasma membrane and inhibition of
internalization, which would also inhibit recycling and degradation.
Alternatively, it could be attributable to inhibition of degradation of
internalized receptors and recycling back to the plasma membrane of
these protected receptors. If inhibition of internalization is the
major mechanism by which IgE mediates FcRI up-regulation, it follows
that (1) IgE should almost completely prevent the decrease
in FcRI expression induced by BFA; and (2) the
up-regulation rate should be equal to the degradation rate. However, if
inhibition of degradation of internalized receptors is the main
mechanism, then one should expect IgE to prevent the decrease in
FcRI expression induced by BFA only in part. We addressed this
question by replotting in Fig. 5, C and D, some
of the data of Fig. 5, A and B. Fig. 5C shows that IgE almost completely prevented the decrease
in FcRI expression induced by BFA. In Fig. 5D, comparison
of the mirror image of the BFA/no IgE curve from Fig. 5A and
the IgE-treated curve from Fig. 5B shows that the rate of
degradation is almost identical (but opposite) to the rate of
up-regulation (p > 0.05, no significant
difference). These results demonstrate that in this in vitro system,
stabilization at the cell surface accounts for the majority of the
up-regulation, providing that basal synthesis is maintained.
In vivo, it is likely that various factors such as IL-4 modulate the
basic mechanism described here. In a study of fetal liver-derived human
mast cells, IL-4 has been reported to synergize with IgE and increase
the percentage of FcRI-positive cells (47). IL-4 has
also been shown to increase IgE-mediated FcRI expression on cord
blood-derived mast cells (23). However, mechanisms for
these effects have not been investigated. It is unlikely that IL-4
would act on the receptor subunits during intracellular processing, at
the cell surface, or after internalization. Rather, the synergy between
IL-4 and IgE is more likely to result from an effect of IL-4 on
transcription of the FcRI subunits, given the fact that numerous
effects of IL-4 are mediated through activation of transcription
factors. An IL-4-induced increase in transcription of the FcRI
subunits would result in an increased availability of receptors that
could be used for IgE-mediated up-regulation and in an increase in
efficiency of up-regulation. This effect would translate into an
increase in the slope of the straight line that describes the
relationship between basal FcRI expression and expression after IgE
treatment (see Fig. 2). Other cytokines could also module the
IgE-mediated up-regulation by affecting the basal level of synthesis of
the receptor subunits.
Conclusions
Our studies show that binding of IgE to the -chain of FcRI
is the minimal requirement to induce IgE-mediated up-regulation of
FcRI on the cell surface, as this regulation does not depend on
transcriptional regulation, hemopoietic-specific factors, or classical
signaling. Rather, up-regulation is the consequence of receptor
stabilization at the plasma membrane, use of recycled and recently
synthesized receptors, and continued basal level of receptor
synthesis.
We propose that the -chain is the primary candidate for initiating
the receptor stabilization that plays a critical role in the
IgE-mediated regulation. First, we show here that the -chain is not
necessary for receptor up-regulation. Second, a primary role for the
-chain in receptor stabilization is unlikely because the -chain
is also part of FcRs, the expression of which is not influenced by
IgG levels. This is based on the observation that mice that are devoid
of B cells and therefore lack Igs, express normal levels of FcRI,
FcRII, and FcRIII (J. Ravetch, unpublished observations).
In contrast, IgE-knockout mice express decreased levels of FcRI
(17, 18). However, a role for the -chain in conjunction
with cannot be ruled out because FcRI cannot be expressed at
the cell surface without . And third, recently reported
crystallography data show a conformational change in FcRI on IgE
binding (48). Although the functional significance of this
conformational change is not known, it is tempting to speculate that it
mediates receptor stabilization. Further studies will be needed to
address this point at the molecular level.
The in vitro system used here was designed and has allowed us to
dissect the minimal requirements for IgE-mediated FcRI
up-regulation. It is likely that in vivo various factors, such as
cytokines, may modulate this basic mechanism.
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Footnotes |
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2 Address correspondence and reprint request to Dr. Jean-Pierre Kinet, Division of Allergy and Immunology, Department of Pathology, Beth Israel Deaconess Medical Center, Research North, 99 Brookline Avenue, Boston MA 02215. E-mail address: jkinet{at}caregroup.harvard.edu
3 Abbreviations used in this paper: BFA, brefeldin A; Endo H, endo--N-acetylglucosamidase; MFI, mean fluorescence intensity.
Received for publication April 16, 2001. Accepted for publication May 25, 2001.
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References |
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  S. C. Pitchford, S. Momi, S. Baglioni, L. Casali, S. Giannini, R. Rossi, C. P. Page, and P. Gresele Allergen Induces the Migration of Platelets to Lung Tissue in Allergic Asthma Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 604 - 612. [Abstract] [Full Text] [PDF]
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D. M. Cauvi, X. Tian, K. von Loehneysen, and M. W. Robertson Transport of the IgE Receptor {alpha}-Chain Is Controlled by a Multicomponent Intracellular Retention Signal J. Biol. Chem., April 14, 2006; 281(15): 10448 - 10460. [Abstract] [Full Text] [PDF]
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 L. M. Ganley-Leal, P. N. Mwinzi, C. B. Cetre-Sossah, J. Andove, A. W. Hightower, D. M. S. Karanja, D. G. Colley, and W. E. Secor Correlation between Eosinophils and Protection against Reinfection with Schistosoma mansoni and the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans Infect. Immun., April 1, 2006; 74(4): 2169 - 2176. [Abstract] [Full Text] [PDF]
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T. Bobrzynski, M. Fux, M. Vogel, M. B. Stadler, B. M. Stadler, and S. M. Miescher A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the Fc{epsilon}RI{alpha} J. Immunol., November 15, 2005; 175(10): 6589 - 6596. [Abstract] [Full Text] [PDF]
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T. Kawakami and J. Kitaura Mast Cell Survival and Activation by IgE in the Absence of Antigen: A Consideration of the Biologic Mechanisms and Relevance J. Immunol., October 1, 2005; 175(7): 4167 - 4173. [Abstract] [Full Text] [PDF]
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S. C. Fish, D. D. Donaldson, S. J. Goldman, C. M. M. Williams, and M. T. Kasaian IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13 J. Immunol., June 15, 2005; 174(12): 7716 - 7724. [Abstract] [Full Text] [PDF]
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 D. MacGLASHAN JR. IgE and Fc{epsilon}RI Regulation Ann. N.Y. Acad. Sci., June 1, 2005; 1050(1): 73 - 88. [Abstract] [Full Text] [PDF]
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R. Schweitzer-Stenner and I. Pecht Cutting Edge: Death of a Dogma or Enforcing the Artificial: Monomeric IgE Binding May Initiate Mast Cell Response by Inducing Its Receptor Aggregation J. Immunol., April 15,&nb |
) or untransfected U937 cells
(
) were cultured in triplicate in the presence of saturating
concentrations of monomeric IgE or vehicle for the indicated times.
Cell surface expression of Fc
).
B, NIH3T3 cells transfected with the 
) or vehicle (
) and assessed for surface expression of
Fc
), or vehicle (
) for the indicated times. B,
IgE-mediated up-regulation uses a pool of preformed receptors and is
dependent on the maintenance of basal levels of receptor synthesis.
U937 cells were cultured in the presence of IgE alone (