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Institut Fédératif de Recherche Necker-Enfants Malades,
*
Unité Mixte de Recherche 8603, Centre National de la Recherche Scientifique/Université Paris-V,
Institut National de la Santé et de la Recherche Médicale, Unité 25, and
Pathology Department, Hôpital Necker-Enfants Malades, Faculté Necker, Université Paris-V, Paris, France
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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R and Fc
R. IgA is present in a significant
proportion among serum Ig and is the main isotype in mucosae, where DC
are numerous. We found that a functional Fc
R (CD89) was expressed in
situ and in vitro on interstitial-type DC but not on Langerhans
cell-type DC. Interstitial-type DC expressed CD89 as a 50- to 75-kDa
glycoprotein with a 32-kDa protein core, which was down-regulated upon
addition of TGF-
1. DC, FcR specifically, bound IgA1 and IgA2.
Cross-linking of CD89 on DC triggered endocytosis in time-dependent
manner. In addition, internalization of polymeric IgA complexes induced
the production of IL-10 and DC activation, as reflected by
up-regulation of CD86 costimulatory molecules, class II MHC expression,
and increased allostimulatory activity. Therefore, interstitial-type DC
may use FcR-mediated Ag sampling in the subepithelium to check
tissue integrity while Langerhans cells inside epithelial layers may
neglect IgA immune complexes. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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R and FcR (1, 2, 3, 4, 5, 6, 7, 8). The latter contribute to
the capacity of DC to process Ags via specific pathways and transfer
them to secondary lymphoid organs.
IgA is the most abundant Ig isotype in mucosal tissues and the second
isotype in the blood compartment representing one-fifth of IgG levels
(9, 10). IgA exists in two subclasses; IgA1 is the
predominant isotype in serum in monomeric form and IgA2 is more
prevalent in mucosal secretions in dimeric form known as secretory IgA
(9, 10). The IgA FcR (FcR or CD89) is expressed on
human blood neutrophils, eosinophils, and monocyte/macrophages as a 55-
to 100-kDa heterogeneously glycosylated protein (11, 12, 13).
CD89 is a type I transmembrane molecule that is encoded by a single
gene located on chromosome 19q13.4 (12, 14). FcR exists
in two known isoforms (a.1 and a.2) differently expressed on blood
monocytes and alveolar macrophages (15). CD89 is a
receptor for IgA1 and IgA2 Abs that binds more polymeric than monomeric
forms (16, 17). Following aggregation of FcR, IgA
immune complexes (IC) can trigger effector cells to perform functions
such as endocytosis, phagocytosis, superoxide release, and release of
cytokines including TNF-, IL-6, and Ab-dependent cellular
cytotoxicity (14, 18, 19, 20, 21).
CD89 is a candidate molecule for Ag uptake by DC, as these cells are
particularly numerous at malpighian epithelial (LC-type DC) plus
subepithelial (interstitial-type DC) barriers, but it is not known
whether human DC bear an IgA receptor. We thus investigated CD89
expression and function on DC and detected functional CD89 molecules on
a subset of DC both in vitro and in vivo. We found that CD89 was
expressed on interstitial-type DC but not detectable on LC in vivo, and
down-regulated by TGF-1 on Langerhans-type DC in vitro. DC FcR
protein bound IgA1 and IgA2 and was quickly internalized upon
aggregation. Cross-linking of polymeric IgA on DC, which mimics the
effect of IC, led to IL-10 production and DC activation.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The following mouse mAb were used: A59 (IgG1
) and A77
(IgG1), specific for FcR (22); IV.3 (IgG2b)
(American Type Culture Collection, Manassas, VA), specific for
FcRII; 3G8 (IgG1), specific for FcRIII; and an irrelevant
IgG1 control (clone 7.1 anti-GST protein). The anti-FcR mAb
My43 (IgM) was a generous gift from Dr. L. Shen (Dartmouth Medical
School, Lebanon, NH). Unconjugated CD68 and HLA-DR, unconjugated and
FITC-labeled CD1a (clone BL6, IgG1) and FITC-labeled HLA-DR were
obtained from Immunotech (Marseille, France). PE-labeled
anti-FcR mAb A59 (A59-PE) and CD86 were obtained from PharMingen
(San Diego, CA). Rabbit anti-mouse Ig Abs were raised in rabbits
immunized with IgG1 (clone A59). F(ab')2 of A59,
A77, and IgG1, and rabbit anti-mouse IgG fractions were prepared
by pepsin digestion (Sigma, St. Louis, MO) and purified on DEAE
columns. FITC-conjugated goat Ab specific for mouse (GAM) and rabbit
Ig, and HRP-conjugated goat anti-rabbit IgG, were obtained from
Southern Biotechnology Associates (Birmingham, AL). IgA myeloma
proteins were purified from patients’ sera as described
(11), and preparations of monomeric and
polymeric IgA1 and an IgA2
(>98% pure) were biotinylated.
IgA1 Fab were obtained by digestion with IgA1 protease as described
(11).
Cell culture
The human monocytic cell line U937 was maintained in RPMI 1640
medium supplemented with 10% FCS, 2 mM glutamine, 100 IU/ml
penicillin, and 100 mg/ml streptomycin (complete medium). In some
experiments, cells were cultured for 18 h with
10-7 M PMA (Sigma). Monocyte-derived
interstitial- and Langerhans cell-type DC were prepared as previously
described (23, 24). Briefly, fresh
CD14+ monocytes were isolated from healthy
volunteers’ PBMC obtained by the standard Ficoll-Paque method and
immediately separated by negative magnetic depletion using
hapten-conjugated CD3, CD7, CD19, CD45RA, CD56, and anti-IgE Abs
(MACS; Miltenyi Biotec, Bergisch Gladbach, Germany) and a magnetic cell
separator (MACS) according to the manufacturer’s instructions. Cells
were cultured in flasks or in 6- or 24-well tissue culture plates
(Costar, Cambridge, MA) for 5–7 days in complete medium supplemented
with 200 ng/ml GM-CSF and 10 ng/ml IL-4, resulting in their
differentiation into CD1a+ interstitial-type DC,
or with GM-CSF, IL-4, and 10 ng/ml TGF-1, resulting in their
differentiation into CD1a+,
E-cadherin+, CLA+,
Langerin+ Lag+, and
Birbeck+ Langerhans cell-type DC.
Flow cytometry
For single- and two-color flow cytometry, 3 x
105 cells were preincubated with 10 mg/ml human
polyclonal IgG to block FcR (22) in 96-well plates
(Becton Dickinson, Mountain View, CA) for 15 min at 4°C in PBS
containing 2% FCS, 0.1% NaN3 and incubated with
mAbs at the appropriate concentration (0.1 mg/ml for anti-CD89
mAbs), or with control isotype-matched irrelevant mAbs at the same
concentration for 20 min at 4°C. After washing, cells were incubated
when appropriate with F(ab')2 GAM-FITC (Southern
Biotechnology Associates) for 15 min at 4°C in the same buffer and
washed again; 104 events were then analyzed with
a FACScalibur (Becton Dickinson) using CellQuest software (Becton
Dickinson). For IgA binding, 105 cells were
preincubated in 96-well plates with human IgG for 15 min at 4°C in
PBS containing 2% FCS, and then incubated for 30 min at 4°C with a
blocking anti-CD89 mAb (100 µl My43 supernatant) or control IgM
hybridoma supernatant, then washed and incubated for 1 h with
biotinylated monomeric or polymeric IgA at 0.1 mg/ml. Cells were washed
again and incubated for 15 min with streptavidin-PE to label-bound IgA.
As a negative control, cells were incubated with a biotinylated IgA1
Fab (11). Cells were analyzed by flow cytometry using a
FACScalibur (Becton Dickinson) and CellQuest software (Becton
Dickinson).
Cell radiolabeling and immunoprecipitation
Cell surface proteins were iodinated with 1 mCi
Na[125I] (Amersham, Arlington Heights, IL)
using the lactoperoxidase method. For FcR immunoprecipitation, cells
(107/ml) were lysed for 30 min at 4°C in PBS
containing 0.5% Nonidet P-40 (Aldrich Chemical, Milwaukee WI), 0.02%
sodium azide, 1% aprotinin, 1 mM diisopropylfluorophosphate, 5 mM
iodoacetamide, and 1 mM PMSF (11). After centrifugation at
14,000 x g for 30 min to remove insoluble material,
cleared lysates were immunodepleted for FcR by using human IgG,
32.2, 3G8, and IV.3 mAb, and precipitated with test mAb as previously
described (15, 22). Bound material was treated or not
treated with N-glycosidase F (Oxford GlycoSystems, Abingdon,
U.K.) and samples were prepared for SDS-PAGE.
RT-PCR analysis
Total RNA was extracted by the acid-phenol procedure and cDNA synthesis and PCR were performed as described previously (15).
Immunohistochemistry
Normal skin and gingival samples were obtained from the tissue bank of the pathology department of Hôpital Necker-Enfants Malades. Serial cryostat sections were prepared and incubated with anti-CD1a (BL1), HLA-DR (B8.12.2), and CD68 (KiM7) from Immunotech, and anti-CD89 (A59, A77) mouse primary Abs, followed by a goat anti-mouse alkaline phosphatase (AP)-conjugated Ab. Double labeling was performed using peroxidase and AP-anti-AP protocols as described elsewhere (25). Fast Blue and 3-amino-9-ethylcarbazole (both from Sigma) were used as substrates for AP and peroxidase, respectively.
Confocal microscopy and endocytosis
Cells were allowed to adhere to glass slides coated with 50 µg/ml poly-L-lysine (Sigma), and consecutively incubated on ice with human polyclonal IgG, mAb A77, and F(ab')2 GAM-FITC (Southern Biotechnology Associates) in PBS containaing 2% FCS. After washing, cells were incubated in complete medium for various times at 37°C or kept on ice. Slides were washed, fixed in 4% paraformaldehyde in PBS, and quenched with 0.1 M glycine. Cells were then incubated for 5 min with 2 µg/ml wheat germ agglutinin (WGA) conjugated to Texas Red and washed again. Mounted slides were examined with a confocal laser microscope system (LSM 510 Carl Zeiss; Zeiss, Jena, Germany).
Activation of DC
DC cultured for 6 days were gently washed and preincubated with blocking anti-CD89 mAb (My43) or irrelevant IgM (clone D6), and then incubated on ice for 60 min with biotinylated IgA, IgG, anti-CD4 mAb, or RPMI 1640–2% human AB serum. Cells were gently washed again and incubated on ice for 20 min with streptavidin-AP to cross-link surface receptors or RPMI 1640–2% human AB serum as negative control. After a final wash, cells were cultured at 5 x 105/ml in complete medium supplemented with 200 ng/ml GM-CSF and 10 ng/ml IL-4. At various times, cells were harvested and their viability, as well as CD86 and DR expression, were assessed by trypan blue exclusion and flow cytometry, respectively.
Allogeneic T cell proliferation
DC cultured for 40 h as described above after incubation
with biotinylated IgA, or RPMI 1640–2% human AB serum and with or
without streptavidin-AP to cross-link surface receptors were collected,
washed three times, resuspended in RPMI 1640 with 10% human AB serum
and added in triplicate at various concentrations to
105 allogeneic T cells/well in 96-well tissue
culture plates (Falcon; Becton Dickinson). T cells were isolated by the
standard Ficoll-Paque method followed by magnetic depletion of non-T
cells (MACS; Miltenyi Biotec). [3H]Thymidine
(Amersham Life Sciences, Buckinghamshire, U.K.) incorporation was
measured in newly synthesized DNA over 18 h, using pulses
initiated at day 5 of the culture with 1 mCi/well of
[3H]thymidine. Cells were then harvested with a
96-well harvester (Pharmacia, St. Quentin, France), collected on
glass-fiber filter (Pharmacia), and the incorporation of thymidine was
measured with a -plate microscintillation counter (LKB,
Pharmacia).
Measurement of IL-10 production by ELISA
Culture supernatants were harvested after 24 and 48 h of culture, and centrifuged twice at 200 x g and 15,000 x g to remove cells and debris. Supernatants were stored at -70°C until cytokine measurements. ELISA was performed in duplicate and according to the manufacturer’s instructions using human quantikine IL-10 (R&D Systems, Minneapolis, MN) and rhIL-10 provided by the manufacturer at 500–7.8 pg/ml. The sensitivity of IL-10 detection was thus 7.8 pg/ml.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The cellular distribution of CD89 in normal skin and mucosae was
investigated by means of immunohistochemistry. Frozen skin and gingival
tissue sections were labeled with anti-CD1a, CD89, DR, or CD68 Abs.
An example of CD1a labeling on LC is shown in Fig. 1
A. An anti-CD89 Ab (A59)
did not stain CD1a+ epidermal LC but labeled
dermal cells on serial sections (Fig. 1B, magnification in
C). Another anti-CD89 Ab (A77) yielded an identical
labeling pattern (not shown). Double labeling with anti-DR (in
blue) and anti-CD89 (in brown) showed two populations of
CD89+ cells in the dermis, one strongly
coexpressing DR (and thus stained bluish red) and the other
DR- (Fig. 1D). Both dermal
populations were CD68+ (not shown). Therefore,
while CD89 was undetectable on LC, dermal macrophages/DC were
CD89+. Similar labeling patterns were observed in
gingival mucosa (Fig. 1E). Absence of CD89 labeling on LC
was not likely to be due to receptor site occupancy, because there was
no LC labeling for IgA on samples from three individuals (data not
shown).
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To investigate the regulation of CD89 expression on DC, we used
freshly isolated CD14+ blood monocytes
differentiated into DC in the presence of GM-CSF and IL-4
(2). These cells share many features with interstitial DC
and particularly with dermal DC, which in the presence of TGF-1,
further differentiate toward the LC phenotype (2, 23, 24, 25).
CD14+ CD1a- peripheral
blood monocytes, CD1a+
E-cadherin- Langerin-
monocyte-derived interstitial-type DC and CD1a+
E-cadherin+ Langerin+
monocyte-derived Langerhans cell-type DC were thus studied for CD89
expression by means of immunofluorescence, SDS-PAGE, and RT-PCR.
Flow cytometry experiments revealed that CD89 expression on
monocyte-derived interstitial-type DC
(CD14low/-
CD1a+ E-cadherin-)
expressed CD89 levels that were significant but lower than those
expressed by monocytes (Fig. 2 and Table I). CD89 expression was barely detectable
on LC-type cells (CD14-
CD1a+ E-cadherin+), with
about 3-fold lower levels than DC-type cells calculated from five
experiments (Fig. 2 and Table I).
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R mAb (A77) F(ab')2 (to avoid
interaction with FcR) from a monocytic cell line (U937),
monocyte-derived DC, and monocyte-derived LC (Fig. 3A). DC CD89 appeared as 50-
to 75-kDa heterogeneously glycosylated molecules. When
immunoprecipitated molecules were digested with
N-glycosidase F, FcR protein was resolved as a major band
of 32 kDa, indicating that monocyte-derived interstitial-type DC and
LC-type DC expressed the same backbone as the CD89 from monocytic cell
line U937 (Fig. 3A). SDS-PAGE also revealed a strong
down-regulation of FcR on the cell surface of LC (Fig. 3A), despite the slightly higher CD1a expression on LC-type
as compared with interstitial-type DC (Fig. 3B). RT-PCR
analysis was then performed and showed that monocyte-derived
interstitial DC and Langerhans cell-type DC expressed the CD89
full-length transcript of 896 bp (a1 transcript) as observed on
monocytes and U937 cells (data not shown) and as previously described
(19). These results indicate that monocyte-derived
interstitial-type DC and LC-type DC expressed the a1 isoform, which is
the main isoform expressed on blood monocytes, neutrophils, and
eosinophils (11, 13, 15).
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Monocyte-derived interstitial- and LC-type DC, and blood monocytes
(used as controls) were then studied for their ability specifically to
bind polymeric and monomeric IgA. To assess binding specificity, cells
were preincubated with a blocking anti-CD89 (My43) Ab or with
irrelevant IgM. Monocytes and monocyte-derived DC bound polymeric
IgA1 (Fig. 4) and to a lesser extent
monomeric IgA1 (data not shown). Both cell types also bound a
myeloma IgA2 and secretory IgA (data not shown). Preincubation of
monocyte-derived interstitial-type DC with My43 Ab inhibited polymeric
IgA1 binding by 60–80% (Fig. 4 and Table II). In contrast, monocyte-derived LC
exhibited very weak polymeric IgA1 binding, which correlates with weak
CD89 expression (Fig. 4 vs Figs. 2
and 3). However, the dim IgA binding
was inhibited by My43 mAb (Fig. 4 and Table II).
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To examine the functional capacity of CD89 on DC, we investigated
whether internalization occurred after FcR cross-linking on
interstitial-type DC using confocal microscopic examination after cell
incubation for various times at 37°C. CD89 cross-linking was
performed with either anti-CD89 plus anti-mouse Ab (both in
F(ab')2 form) (Fig. 5) or polymeric IgA (not shown), on
poly-L-lysine-coated slides. As shown in Fig. 5A, CD89 was
only detected at the plasma membrane, colocalizing with WGA labeling on
cells kept at 4°C, whereas the majority of CD89 labeling was
intracellular after 15 min of incubation at 37°C (Fig. 5B). In contrast, after 1 h at 37°C, cross-linked
CD89 molecules were found at the periphery, near the plasma membrane
(Fig. 5C), pointing to receptor recycling.
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in culture. Cells were incubated at 4°C with TNF-, biotinylated
polymeric IgA1 (0.1–0.01 mg/ml), biotinylated IgG at the same
concentration or biotinylated anti-CD4 mAb (negative control), and
then with or without a cross-linker, streptavidin coupled to a carrier
molecule (AP). Cells were then washed and cultured for various times.
As shown in Fig. 6A, while IgA
and IgG alone (c and e) failed to activate DC,
cross-linking of IgA and IgG (d and f) induced
CD86 expression on 
40% of cells. As a positive control, similar
activation was observed after cell exposure to 10 ng/ml TNF- (Fig. 6A, a). In contrast, CD4 cross-linking under the
same conditions did not significantly activate DC (Fig. 6A,
b). It is noteworthy that DC activation through IgA
complexes was specific to FcR as the preincubation of cells with a
blocking anti-CD89 mAb (My43) inhibited their activation by IgA but
not by IgG complexes (Fig. 6A, dashed histograms in
d and f). Therefore, we performed time-course
experiments to analyze by flow cytometry the percentage of
double-positive cells expressing high levels of MHC class II (DR) and
CD86 molecules in culture (Fig. 6B). IgA complexes induced
maximal activation after 2 days of culture in a manner
comparable to TNF-. This was still observed with 0.01 mg/ml of
cross-linked IgA (Fig. 6B). This IgA-mediated activation was
specific for FcR as it was inhibited by My43 mAb and was not
observed for anti-CD4 cross-linking (Fig. 6B). IgA
complexes did not increase costimulatory molecule (CD86) and MHC class
II expression on LC-type cells (data not shown). This is in accordance
with the very weak expression of CD89 and binding of IgA on these cells
(
Figs. 1–4).
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To examine whether CD89-mediated phenotypic activation of
interstitial-type DC was associated with their function, we focused on
their capacity to trigger allogeneic lymphocyte activation and to
produce IL-10. The results showed that preincubation of DC with IgA
complexes significantly increased the proliferation of allogeneic
T-lymphocytes at low stimulator/effector ratio (250–1000 DC for
105 T cells; Fig. 7A). These effects required
the cross-linking of CD89, because IgA alone did not have any
effect, and was specific to CD89 because it was abrogated by
preincubating cells with anti-CD89 My43 mAb (Fig. 7A).
Binding of IgA complexes may thus contribute to the functional
maturation of immature interstitial-type DC.
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and IL-1 (26). Therefore, we
examined the ability of interstitial-type DC to produce IL-10 after
stimulation via CD89 by IgA complexes. Binding of cross-linked IgA
induced the production of IL-10 at comparable level to that observed
with stimulation by TNF- and IL-1, while TNF- alone failed to
induce significant IL-10 production (Fig. 7B). This effect
was abrogated by preincubation with My43 and required receptor
aggregation as IgA alone failed to induce IL-10 release (Fig. 7B). |
Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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1 induces further differentiation toward LC
(23, 24). Using this model, we also observed that
interstitial-type DC expressed heterogeneously glycosylated a1 isoform
of the CD89 that was functional, whereas CD89 expression by Langerhans
cell-type DC was weak.
The unique cytokine microenvironment in the epithelium plays an
important role in regulating the DC phenotype. We and others have shown
that TGF-1, which is produced by keratinocytes in vivo
(27), is activated in a tissue-specific manner, and is
responsible for the unique phenotype of LC (23, 24, 28).
In the present study, CD89 was detected in vivo on dermal cells, but
not on LC. Monocyte-derived interstitial-type DC (cultured in the
absence of TGF-1) express CD89 albeit at lower levels than
monocytes, while CD89 expression appears to be further down-regulated
in monocyte-derived LC-type DC that are obtained by addition of
TGF-1. Furthermore, TGF-1 has been shown to down-regulate IgA
Fc-receptor (CD89) expression on human monocytes (29).
Therefore, it is likely that TGF-1 is responsible for the
down-regulation of CD89 on LC in human skin and gingival mucosa. The
lack of CD89 labeling on LC in situ does not rule out weak
expression.
Our results thus point to developmental regulation of CD89 expression
on DC, and we were concerned with the potential physiological
significance of this observation. We show that CD89 is a selective
Ag-binding and Ag-uptake receptor that permitted internalization of its
ligand by immature DC, triggered the expression of the costimulatory
molecule CD86 and of MHC class II molecules at the plasma membrane,
increased their allostimulatory activity and triggered IL-10
production. IgA plays a major role in preventing pathogen adhesion to
the mucosa, and pathogen-IgA IC are washed out by mucosal secretion.
However, one can expect that following mucosal lesions IgA IC could
play a role in Ag sampling and presentation by DC in vivo, as well as
in DC activation, depending on the site of Ag entry. Indeed,
cross-linking of IgA bound to its receptor on interstitial-type DC
resulted in internalization after 15 min, indicating that FcR
efficiently delivers Ag to the endosomal compartment. A second event
that followed cross-linking of IgA bound to its receptor on DC was the
up-regulation of the costimulatory molecule CD86 and membrane MHC class
II Ags. Therefore, CD89 triggering by polymeric IgA complexes activates
DC. Following this, activated DC efficiently triggered the
proliferation of allogeneic lymphocytes at a low stimulator/effector
ratio. Interestingly, CD89 aggregation on interstitial-type DC by IgA
complexes also induced IL-10 production. IL-10 has been shown to
mediate IgA1 and 2 isotype switching (30). Thus,
activation of DC via CD89 may act in positive feedback on IgA
production. Taken together, our data extend the known functions
described for CD89 on myeloid cells including endocytosis,
phagocytosis, superoxide production, Ab-dependent cellular
cytotoxicity, and release of proinflammatory cytokines (e.g., TNF-
and IL-6; Refs. 14 and 18, 19, 20, 21).
The above results, obtained using in vitro-derived DC, may be relevant
to physiological situations because in vitro monocyte-derived
interstitial type DC, and monocyte-derived LC-type DC were found to
resemble in vivo interstitial DC and LC respectively
(23, 24, 25). In vivo, interstitial-type DC are located
beneath the epithelium, within the parenchyma of organs, and in blood.
The presence of IgA IC in interstitial tissues or blood may thus result
from either breakdown of the epithelial barrier or a blood-borne
infection. Our results suggest that, in these circumstances, IgA IC may
lead to Ag internalization by interstitial DC, followed by their
activation and subsequent Ag presentation to T cells. In contrast,
because CD89 expression is down-regulated by TGF-1 and undetectable
by immunohistochemical methods on human epithelial LC in situ, our
results suggest that LC may neglect IgA IC within the epithelium in the
absence of a breakdown of the epithelial barrier.
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Acknowledgments |
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Footnotes |
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2 F.G. and P.L. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Frédéric Geissmann, Unité Mixte de Recherche 8603, Centre National de la Recherche Scientifique, Hôpital Necker-Enfants Malades, 161 rue de Sèvres, 75743 Paris Cedex 15, France.
4 Abbreviations used in this paper: DC, dendritic cells; LC, Langerhans cells; IC, immune complexes; GAM, goat Ab specific for mouse; WGA, wheat germ agglutinin; AP, alkaline phosphatase; MFI, mean fluorescence intensity.
Received for publication July 14, 2000. Accepted for publication October 5, 2000.
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References |
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1, in the presence of GM-CSF and IL-4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187:961.1 prevents the non-cognate maturation of human dendritic Langerhans cells. J. Immunol. 162:4567. receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J. Exp. Med. 189:371.1 in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. Proc. Natl. Acad. Sci. USA 90:6076.1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157:1499.[Abstract]
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E. Merck, B. de Saint-Vis, M. Scuiller, C. Gaillard, C. Caux, G. Trinchieri, and E. E. M. Bates Fc receptor {gamma}-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses Blood, May 1, 2005; 105(9): 3623 - 3632. [Abstract] [Full Text] [PDF]
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V. Decot, G. Woerly, M. Loyens, S. Loiseau, B. Quatannens, M. Capron, and D. Dombrowicz Heterogeneity of Expression of IgA Receptors by Human, Mouse, and Rat Eosinophils J. Immunol., January 15, 2005; 174(2): 628 - 635. [Abstract] [Full Text] [PDF]
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B. Pasquier, Y. Lepelletier, C. Baude, O. Hermine, and R. C. Monteiro Differential expression and function of IgA receptors (CD89 and CD71) during maturation of dendritic cells J. Leukoc. Biol., December 1, 2004; 76(6): 1134 - 1141. [Abstract] [Full Text] [PDF]
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N. J. Mantis, S. A. Farrant, and S. Mehta Oligosaccharide Side Chains on Human Secretory IgA Serve as Receptors for Ricin J. Immunol., June 1, 2004; 172(11): 6838 - 6845. [Abstract] [Full Text] [PDF]
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A. M. Woltman, N. Schlagwein, S. W. van der Kooij, and C. van Kooten The Novel Cyclophilin-Binding Drug Sanglifehrin A Specifically Affects Antigen Uptake Receptor Expression and Endocytic Capacity of Human Dendritic Cells J. Immunol., May 15, 2004; 172(10): 6482 - 6489. [Abstract] [Full Text] [PDF]
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P. J. Tacken, K. L. Hartshorn, M. R. White, C. van Kooten, J. G. J. van de Winkel, K. B. M. Reid, and J. J. Batenburg Effective Targeting of Pathogens to Neutrophils via Chimeric Surfactant Protein D/Anti-CD89 Protein J. Immunol., April 15, 2004; 172(8): 4934 - 4940. [Abstract] [Full Text] [PDF]
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 R. Reljic, C. Crawford, S. Challacombe, and J. Ivanyi Mouse IgA inhibits cell growth by stimulating tumor necrosis factor-{alpha} production and apoptosis of macrophage cell lines Int. Immunol., April 1, 2004; 16(4): 607 - 614. [Abstract] [Full Text] [PDF]
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J. Rey, N. Garin, F. Spertini, and B. Corthesy Targeting of Secretory IgA to Peyer's Patch Dendritic and T Cells after Transport by Intestinal M Cells J. Immunol., March 1, 2004; 172(5): 3026 - 3033. [Abstract] [Full Text] [PDF]
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R. J. Pleass, S. A. Ogun, D. H. McGuinness, J. G. J. van de Winkel, A. A. Holder, and J. M. Woof Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection Blood, December 15, 2003; 102(13): 4424 - 4430. [Abstract] [Full Text] [PDF]
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Z. Banki, L. Kacani, B. Mullauer, D. Wilflingseder, G. Obermoser, H. Niederegger, H. Schennach, G. M. Sprinzl, N. Sepp, A. Erdei, et al. Cross-Linking of CD32 Induces Maturation of Human Monocyte-Derived Dendritic Cells Via NF-{kappa}B Signaling Pathway J. Immunol., April 15, 2003; 170(8): 3963 - 3970. [Abstract] [Full Text] [PDF]
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 E. Haddad, I. C. Moura, M. Arcos-Fajardo, M.-A. Macher, V. Baudouin, C. Alberti, C. Loirat, R. C. Monteiro, and M. Peuchmaur Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schonlein Nephritis: Association between CD71 Expression and IgA Deposits J. Am. Soc. Nephrol., February 1, 2003; 14(2): 327 - 337. [Abstract] [Full Text] [PDF]
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C. Sedlik, D. Orbach, P. Veron, E. Schweighoffer, F. Colucci, R. Gamberale, A. Ioan-Facsinay, S. Verbeek, P. Ricciardi-Castagnoli, C. Bonnerot, et al. A Critical Role for Syk Protein Tyrosine Kinase in Fc Receptor-Mediated Antigen Presentation and Induction of Dendritic Cell Maturation J. Immunol., January 15, 2003; 170(2): 846 - 852. [Abstract] [Full Text] [PDF]
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N. J. Mantis, M. C. Cheung, K. R. Chintalacharuvu, J. Rey, B. Corthesy, and M. R. Neutra Selective Adherence of IgA to Murine Peyer's Patch M Cells: Evidence for a Novel IgA Receptor J. Immunol., August 15, 2002; 169(4): 1844 - 1851. [Abstract] [Full Text] [PDF]
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S. Andreae, F. Piras, N. Burdin, and F. Triebel Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223) J. Immunol., April 15, 2002; 168(8): 3874 - 3880. [Abstract] [Full Text] [PDF]
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H. C. Heystek, C. Moulon, A. M. Woltman, P. Garonne, and C. van Kooten Human Immature Dendritic Cells Efficiently Bind and Take up Secretory IgA Without the Induction of Maturation J. Immunol., January 1, 2002; 168(1): 102 - 107. [Abstract] [Full Text] [PDF]
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I. C. Moura, M. N. Centelles, M. Arcos-Fajardo, D. M. Malheiros, J. F. Collawn, M. D. Cooper, and R. C. Monteiro Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)A1 Receptor and Its Enhanced Expression on Mesangial Cells in IgA Nephropathy J. Exp. Med., August 13, 2001; 194(4): 417 - 426. [Abstract] [Full Text] [PDF]
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) is restricted to dermal cells and CD1a (
) or after stimulation
(see Materials and Methods) with PBS (
), biotinylated
anti-CD4 Ab cross-linked with streptavidin-AP (
), 0.1 mg/ml
biotinylated IgA1
), or blocking anti-CD89
(My43) mAb followed by 0.1 mg/ml biotinylated IgA1
). Data are from the same experiment as in Fig. 5
), or
biotinylated IgA1
) or
with preincubation with the blocking anti-CD89 Ab My43 (
). Cells
were then cultured for 5 days with allogeneic T cells, and
[3H]thymidine incorporation was measured over 18 h.
B, Fc