Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T lymphocytes and association of fyn tyrosine kinase with Fc epsilon RII/CD23.

Despite the evidence for the expression of Fc epsilon RII/CD23, a glycoprotein that is a low-affinity Fc receptor for IgE, obtained on T cell lines and some pathological T cells, that of Fc epsilon RII/CD23 on normal human T cells is still unclear. We studied the emergence of T cells bearing Fc epsilon RII/CD23 in short-term culture of normal human peripheral blood mononuclear cells stimulated with 15 microliters/ml phytohemagglutinin (PHA). Using two-dimension flow cytometry, more than 10% of Fc epsilon RII/CD23(+) cells were shown to co-express CD3 antigen. Both CD4(+) and CD8(+) T cells expressed Fc epsilon RII/CD23. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4 stimulated PBMC was demonstrated by northern blotting and in-situ hybridization. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the human natural killer-like cell line YT, activation of which was easily detected by the induction of interleukin-2 receptor/p55 (Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody enhanced IL-2R/p55 expression on YT cells transfected with Fc epsilon RII cDNA (YTSER). A possible involvement of protein-tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied using YTSER. Fc epsilon RII was physically associated with an src-family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple function of p59fyn which may be implicated in the Fc epsilon RII-mediated activation signal in YT cells.     

Soluble Fc epsilon R II levels in normal children and patients with immunodeficiency diseases

CD23 is expressed on mature B cells and is identical to a low-affinity IgE Fc epsilon receptor type II (Fc epsilon R II). The C terminal portion of CD23 is released to the serum as soluble Fc epsilon R II (sFc epsilon R II), which may be involved in regulation of IgE synthesis. We studied sFc epsilon R II levels in normal children and in patients with immunodeficiencies, including common variable immunodeficiency (CVI), partial DiGeorge syndrome, and immunodeficiency associated with ectodermal dysplasia to examine the relationship of sFc epsilon R II levels to B cell numbers and other immunoparameters. Serum Fc epsilon R II levels are higher in younger children (younger than 3 years) and decline gradually with age. In 11 patients with CVI with normal numbers of B cells (greater than 6%), sFc epsilon R II levels were comparable to that of control subjects. Five patients with CVI with deficiencies of peripheral B cells had levels of sFc epsilon R II similar to levels of control subjects. In all but one patient with partial DiGeorge syndrome, sFc epsilon R II levels were not significantly elevated, despite the presence of elevated peripheral B cell numbers. Of six patients with ectodermal dysplasia, four demonstrated increased Fc epsilon R II levels, a finding not correlated with serum IgE levels or with peripheral eosinophil or B cell numbers.     

Affinity-purified soluble Fc epsilon RII/CD23 derived from RPMI-8866 cells induces histamine release from human nasal polyp mast cells through a non-IgE-mediated mechanism.

Soluble Fc epsilon RII/CD23 (IgE-binding factor) is released spontaneously from activated B cells and most EBV-immortalised B cell lines. We have purified soluble Fc epsilon RII/CD23 from culture supernatants of RPMI-8866 cells on an IgE Sepharose column, and studied its ability to release histamine from human nasal polyp mast cells. Soluble Fc epsilon RII/CD23 induces release of a significant amount of histamine from nasal polyp mast cells in a dose-dependent manner. IgE, and a monoclonal antibody specific for the soluble form of this receptor, were shown to neutralise this effect. It was found that soluble Fc epsilon RII/CD23 was still capable of triggering histamine release from nasal polyp mast cells from which IgE had been eluted by incubation in a low pH buffer, suggesting that a non-IgE mediated mechanism was responsible for this effect.     

TNF-α Regulates GM-CSF-, IL-3- or M-CSF-Induced Fc ε RII/CD23 Gene Expression and Soluble Fc ε RII Release by Human Monocytes

The authors examined the regulatory effects of tumour necrosis factor-α (TNF-α) on granulocyte macrophage colony stimulating factor (GM-CSF)-, interleukin-3 (IL-3)- or macrophage colony stimulating factor (M-CSF)-induced gene expression of the low affinity receptor for IgE (Fc ε RII) on human monocytes and GM-CSF-, IL-3- or M-CSF-induced soluble Fc ε RII (sFc ε RII) release from monocytes. The expression of GM-CSF-, IL-3- or M-CSF-induced Fc ε RII on the surface of monocytes was reduced by TNF-α. The present analysis was designed to examine whether or not TNF-α could suppress GM-CSF-, IL-3- or M-CSF-induced Fc ε RII messenger RNA (mRNA) expression and enhance the release of sFc ε RII induced by these cytokines. The addition of TNF-α to monocyte cultures with GM-CSF, IL-3 or M-CSF significantly reduced Fc ε RII expression on the surface of monocytes and significantly increased sFc ε RII release from monocytes. These results suggest that TNF-α-dependent reduction of GM-CSF-, IL-3- or M-CSF-induced Fc ε RII expression on the surface of monocytes resulted, at least in part, from the suppression of Fc ε RII mRNA and the enhancement of sFc ε RII release.     

Co-crosslinking Fc epsilon RII/CD23 and B cell surface immunoglobulin modulates B cell activation.

Previous studies have shown that a highly multivalent from of anti-IgD or anti-IgM, prepared by conjugating the respective antibodies to dextran, causes extensive B cell proliferation with ng/ml concentrations of the anti-immunoglobulin (Ig). A modification of this system has been exploited to investigate the effect of co-crosslinking the Fc epsilon RII and surface Ig by binding DNP to the dextran backbone (DNP-dextran) and employing a DNP-specific monoclonal IgE of either rat or mouse origin. Addition of anti-IgD-(H delta a/1)[DNP-dextran] or anti-IgM-[DNP-dextran] to purified, resting murine B cells resulted in B cell proliferation over a broad dose (0.03-30 micrograms/ml). Addition of DNP-specific rat or mouse IgE dramatically modulated the proliferative response. Proliferation in response to doses greater than 0.3 microgram/ml H delta a/1-[DNP-dextran] was consistently reduced in a dose-dependent manner in the presence of increasing amounts of IgE while proliferation to lower concentrations of H delta a/1-[DNP-dextran] was slightly enhanced or not influenced at all by the IgE anti-DNP. Interleukin-4 (IL-4) significantly increased the IgE effect, in line with its known enhancing effects on Fc epsilon RII levels. Experiments measuring Ig production rather than proliferation demonstrated that in the presence of IgE anti-DNP, B cells produced lower amounts of immunoglobulin (IgG1 or IgM) in response to an anti-Ig signal. Control experiments demonstrated that the IgE effect on proliferation was blocked by monoclonal anti-Fc epsilon RII, but not anti-Fc gamma RII, thus demonstrating the necessity for IgE/Fc epsilon RII interaction. In addition, the necessity for co-crosslinking was shown by the inability of IgE anti-DNP to affect the proliferative response to H delta a/1-dextran even in the presence of various doses of DNP-dextran. These results demonstrate that co-crosslinking of sIg and the Fc epsilon RII results in an altered B cell response to anti-Ig mediated activation. IL-4 does not ablate this inhibition, in contrast to the effect of co-crosslinking Fc gamma RII and surface Ig, suggesting a model whereby IgE can modulate its own production.     

Tumour necrosis factor-alpha augments the expression of Fc IgE receptor (Fc epsilon RII/CD23) on human monocytic cell lines and down-regulates interleukin-4-driven Fc epsilon RII expression on monocytes.

We investigated the expression of the low affinity Fc IgE receptor (Fc epsilon RII/CD23) on the human monocytic cell lines U937, THP-1, Mono-Mac-6, and cultured human peripheral blood monocytes under stimulation with human tumour necrosis factor-alpha (TNF-alpha) and other cytokines. Fc epsilon RII was demonstrated by flow cytometry analysis employing the anti-Fc epsilon RII monoclonal antibody 3-5. TNF-alpha alone had a weak but significant stimulating effect on the Fc epsilon RII expression on the cell lines U937 and THP-1, and very modestly on Mono-Mac-6 cells. TNF-alpha strongly synergized with interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). IFN-alpha per se was ineffectual, but was able to increase the TNF-alpha effect. Furthermore, the action of TNF-alpha was slightly augmented by human IL-6. Similar effects were noted with TNF-beta alone or in combination with other cytokines. Interestingly, on human monocytes TNF-alpha weakly reduced the basal level of Fc epsilon RII, and markedly diminished the IL-4-induced Fc epsilon RII expression. Our results indicate that several cytokines may interact in a cytokine network to modulate Fc epsilon RII expression on monocytic cell lines. On human blood monocytes, TNF-alpha, like IFN-gamma or IL-6, counteracts the IL-4-induced Fc epsilon RII expression. These data suggest different regulatory pathways of Fc epsilon RII expression on blood monocytes and myelomonocytic cell lines.     

Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23).

Recent studies have established that the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) is a structurally and functionally unique immunoglobulin receptor. DNA sequence analysis predicts that, in contrast to other FcR, Fc epsilon RII is not a member of the immunoglobulin gene superfamily and, indeed, is inserted into the membrane in opposite orientation from most other membrane proteins. While the Fc epsilon RII of macrophages, eosinophils, and platelets mediate IgE-dependent cytotoxicity and promote phagocytosis of IgE-antigen complexes, the function of Fc epsilon RII on B lymphocytes remains unclear. Much effort has been directed toward establishment of its role in IgE regulation, but the plurality of B cell Fc epsilon RII expression, i.e. greater than 90% of the mu + /delta + B lymphocytes, is incongruous with simply a role in regulating only IgE responses. Hence, the discovery that Fc epsilon RII is identical to the B-cell activation antigen, CD23, together with its novel structural features, suggests an additional more important role for this interesting protein and would explain the disparity between a commonly expressed receptor with apparently limited functions.     

Fc epsilon receptor II/CD23-positive lymphocytes in atopic dermatitis. I. The proportion of Fc epsilon RII+ lymphocytes correlates with the extent of skin lesion.

Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood from patients with atopic dermatitis and with eczematous dermatitis, and normal non-atopic subjects by using monoclonal antibodies to human lymphocyte Fc epsilon RII, and to lymphoid cell-surface antigens by immunofluorescence staining. Based on the extent of the dermatitis patients were classified as severe (greater than 50% skin surface involved), moderate (50-10%) and mild (less than 10%). Patients with severe and moderate atopic dermatitis had 5.9% and 5.7% Fc epsilon RII+ peripheral blood mononuclear cells (PBMC), respectively, that were significantly higher than percentages in mild atopic dermatitis patients (2.6%), severe to moderate eczematous dermatitis patients (2.3%), mild eczematous dermatitis patients (2.2%) and normal individuals (1.7%)(0.05 greater than P). In severe and moderate atopic dermatitis patients, 10% of Fc epsilon RII+ PBMC were T cells that preferentially expressed CD8, and the remainder B cells and monocytes. Fc epsilon RII+ T cells comprised 1% of peripheral T cells, while half or more of peripheral B cells expressed Fc epsilon RII. In mild atopic dermatitis patients, eczematous dermatitis patients and normal subjects. Fc epsilon RII were expressed exclusively on 25-35% of peripheral B cells. Short-term treatment and long-term follow-up of atopic dermatitis patients revealed that changes in the skin condition were related closely to fluctuations in the proportion of Fc epsilon RII+ PBMC. Total serum IgE levels and atopic respiratory allergy did not influence the percentage of Fc epsilon RII+ PBMC. These findings suggest that the percentage of Fc epsilon RII+ PBMC reflects the extent of atopic dermatitis.     

Characterization of new rat anti-mouse IgE monoclonals and their use along with chimeric IgE to further define the site that interacts with Fc epsilon RII and Fc epsilon RI.

Three rat monoclonal antibodies specific for mouse IgE (C12B9, 23G3, and B1E3) were established by using monoclonal anti-DNP mouse IgE (mIgE) as immunogen. These antibodies, as well as a fourth, (R1E4) were characterized. It was found that one antibody (C12B9) recognizes an allotypic determinant (Igh-7a) found on the C epsilon chain of mIgE. Antibody cross-blocking studies and epitope mapping studies using recombinant mIgE indicated that 3 antibodies (C12B9, R1E4 and 23G3) were directed against the C epsilon 3 domain while one (B1E3) was directed against the C epsilon 4 domain. A highly specific sandwich RIA for mIgE was developed using these antibodies. Use of these monoclonal anti-mIgE antibodies in conjunction with recombinant chimeric mIgE-human IgG1 molecules, demonstrated that the C epsilon 3 domain is important in the binding of mIgE to the murine B cell Fc epsilon RII as well as to the murine mast cell F epsilon RI. The presence of the C epsilon 4 domain influenced the binding of the recombinant IgE to the Fc epsilon RII; in contrast to the C epsilon 4 domain had no effect on binding to the Fc epsilon RI.     

Quantitative and qualitative analysis of the Fc receptor for IgE (Fc epsilon RII) on human eosinophils

In order to characterize the Fc receptor for IgE (Fc epsilon RII) on human eosinophils, we have compared the binding of human IgE myeloma protein to that of a monoclonal antibody (mAb BB10) directed against a common antigenic determinant of the Fc epsilon RII present on eosinophils, platelets and macrophages. Scatchard analysis of the binding to human eosinophils of the BB10 mAb revealed a linear monophasic binding curve, with a binding affinity of 1.17 x 10(7) M-1 and a number of 10(5) binding sites per cell. Biochemical analysis of the human eosinophil Fc epsilon R, performed by immunosorbent chromatography with either BB10 mAb or IgE, showed under nonreducing conditions a major component of 200 kDa. Under reducing conditions, 3 peptide fragments were obtained, with molecular masses of 45-50, 23 and 15 kDa. Finally, comparative analysis suggested that the Fc epsilon RII of human eosinophils and of a human macrophage cell line (U937) are structurally related and differ from the high-affinity Fc epsilon RI present on basophilic granulocytes.     

Studies on the role of interleukin-4 and Fc epsilon RII in the pathogenesis of minimal change nephrotic syndrome.

Childhood minimal change nephrotic syndrome (MCNS) has often been associated with allergic symptoms such as urticaria, bronchial asthma, atopic dermatitis, allergic rhinitis and elevated IgE levels and referred to involve immune dysfunction. Fc epsilon RII is known to be involved in IgE production and response. Interleukin-4 is being recognized as a major cytokine up-regulating IgE production. Hence the present study is aimed at investigating the role of interleukin-4 and Fc epsilon RII in the pathogenesis of MCNS. IgE was measured by ELISA. Fc epsilon RII was analyzed by fluorescence activated cell scanner (FAC-scan) by double antibody staining with anti Leu16-FITC and anti Leu20-PE. Soluble IgE receptor was measured by ELISA using anti CD23 antibody (3-5-14). Interleukin-4 activities were measured by CD23 expression on purified human tonsillar B cells. Serum IgE levels were significantly higher in MCNS (1,507 +/- 680 IU/dl) than in normal controls (123 +/- 99.2 IU/dl). A significantly higher expression of membrane Fc epsilon RII was noted for MCNS (41 +/- 12%) than that in normal controls (18 +/- 6.2%) (p < 0.001). Soluble CD23 levels were also significantly higher in MCNS (198 +/- 39.3%) than in normal controls (153 +/- 13.4) (p < 0.01). Interleukin-4 activity in sera of MCNS (12U/ml) was also significantly higher than normal controls (4.5U/ml). These results indicate that increased production of Fc epsilon RII and interleukin-4 may play an important role in the pathogenesis of MCNS.     

Human B cells cannot be triggered to kill target cells through their Fc gamma RII or Fc epsilon RII receptors.

There has been some controversy as to whether or not B cells can kill target cells through their Fc receptors. To address this, we have examined the ability of human B cells from a variety of sources to lyse hybridoma cells with specificity for either the B cell Fc gamma RII or Fc epsilon RII using a reverse killing assay, as well as their ability to lyse opsonized chicken erythrocytes using a classic ADCC assay. Tonsil B cells, chronic lymphocytic leukemia B cells, and Epstein-Barr virus-induced B cells, even after preactivation with a cocktail of cytokines, all failed to lyse any of these targets. We conclude that Fc gamma RII and Fc epsilon RII on human B cells are not cytotoxic trigger molecules.     

Fc epsilon receptor II/CD23+ lymphocytes in atopic dermatitis. III. Aberrant control in the in vitro expression of Fc epsilon RII/CD23 on peripheral blood T cells in atopic dermatitis.

In vitro Fc epsilon RII expression was examined in patients with atopic dermatitis, those with non-atopic eczematous dermatitis and normal individuals following stimulation of peripheral blood cells with recombinant IL-4 (rIL-4), phytohaemagglutinin (PHA), or PHA plus rIL-2. At various days cells were stained with MoAbs to human lymphocyte Fc epsilon RII and to lymphoid cell-surface antigens and analysed by flow cytometry. rIL-4, but not rIL-2, specifically induced Fc epsilon RII on T cells as well as B cells in atopic dermatitis, eczematous dermatitis and normal individual groups. Both atopics and non-atopics generated comparable proportions of Fc epsilon RII+ T cells (T epsilon cells), whereas the frequency of B cells bearing Fc epsilon RII(B epsilon cells) was significantly higher in patients with extensive atopic dermatitis than in those with mild atopic dermatitis and other subjects. Comparable levels of T epsilon cells were detected in both atopic and non-atopic donors following stimulation of peripheral blood cells with PHA or pre-activation of the cells with PHA plus subsequent incubation with rIL-2. Whereas both CD8+ and CD4+ subsets were present in T epsilon cell populations induced specifically by rIL-4, PHA and PHA plus rIL-2, patients with atopic dermatitis had a greater tendency for Fc epsilon RII expression on CD8+ T cells compared with patients with eczematous dermatitis and normal individuals. Recombinant interferon-gamma (rIFN-gamma), but not rIFN-alpha or prostaglandin E2 (PGE2), suppressed the generation of T epsilon cells by rIL-4 in atopics and non-atopics to the same degree. These results suggest the aberrant control of Fc epsilon RII expression on T cells, especially those bearing CD8, in atopic dermatitis.     

Production of IgE-potentiating factor in man by T cell lines bearing Fc receptors for IgE

The regulation of human IgE production in vitro by soluble T cell factors was examined. T cells were isolated from the peripheral blood of 2 patients with the hyper-IgE syndrome on the basis of their expression of Fc receptors for human IgE (Fc epsilon R). The T cells were incubated with human myeloma IgE (10 micrograms/ml), washed, reacted with immunosorbent-purified goat anti-human IgE conjugated with fluorescein isothiocyanate, and then separated into Fc epsilon R+ and Fc epsilon R- T cells on the fluorescence-activated cell sorter. Fc epsilon R+ T cells and Fc epsilon R- T cells were propagated in culture using supernatants of phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) and irradiated autologous PBMC. Supernatants of Fc epsilon R+ T cell lines but not of Fc epsilon R- T cell lines selectively enhanced IgE synthesis in cultures of B cells obtained from patients with allergic rhinitis but not from normal nonallergic subjects. The surface phenotype of the Fc epsilon R+ T cell line was predominantly T3+, T4+, Ia+ with few (15%) T8+ cells. Two T cell clones were grown from the Fc epsilon R+ T cell line by limiting dilution (0.3 cells/well). These clones possessed the T4+ helper/inducer phenotype and secreted IgE-enhancing factor(s). The IgE-enhancing factor(s) which had affinity for insolubilized human IgE was sensitive to treatment with trypsin and neuraminidase, and had as its target an IgE-bearing B cell. These results suggest that a subset of human T cells bearing an Fc epsilon R secretes an IgE-binding glycoprotein which selectively enhances IgE synthesis by IgE-bearing B cells.     

Regulation of the expression of the low-affinity IgE receptor (Fc epsilon RII) in the human monocyte-like cell line U-937 by phorbol esters and IgE

The expression of the low-affinity receptor for IgE Fc epsilon RII) in the human monocyte-like U-937 cell line can be upregulated by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and by IgE. TPA induces terminal differentiation of U-937 cells and causes a four- to fivefold increase in the number of Fc epsilon RII. TPA also modulates the expression of several other membrane markers of U-937 cells. IgE alone has a modest effect on the expression of Fc epsilon RII (about a 10% increase), while simultaneous treatment of U-937 cells with TPA and IgE has a cooperative effect, causing an eightfold increase in the number of Fc epsilon RII. Cycloheximide strongly suppresses the expression of Fc epsilon RII, both in TPA-stimulated and unstimulated cells; this effect can be partly reversed by culturing the cells in the presence of IgE. These results suggest that TPA induces the expression of newly synthesized receptors, while IgE causes an accumulation of preformed receptors.     

Human Fc epsilon R II and IgE-binding factors

The low-affinity receptor for IgE (Fc epsilon R II) is mainly expressed on B lymphocytes, although it may also be found on some monocytes, eosinophils, and platelets. The presence of Fc epsilon R II on T cells is still controversial, but our results demonstrate that it is expressed on some HTLV-I-transformed T lymphocytes, and they strongly suggest that it may be found on a small proportion of normal T cells. Fc epsilon R II is a 45-KD glycoprotein containing one N-linked carbohydrate of complex type, O-linked carbohydrates, and sialic acid residues. Fc II is cleaved into soluble fragments with molecular weights of 37, 33, 25, and 12 KD, the first three retain the ability of binding to IgE, i.e., they are IgE-binding factors (IgE-BFs). The enzymes involved in their proteolytic cleavage are cell bound. The cDNA coding for Fc epsilon R II was cloned and functionally expressed. The predicted sequence has no homology with that of murine IgE-BFs which are of T cell origin. However, there is a striking homology with several animal lectins, and since the IgE-binding site is located in the homology region, it is possible that it binds to IgE via the carbohydrates expressed on the Fc region of this immunoglobulin. The expression of Fc epsilon R II on B cells and the release of IgE-BFs are upregulated by interleukin 4 and suppressed by gamma and alpha interferons.(ABSTRACT TRUNCATED AT 250 WORDS)     

IgE class-specific regulatory factor(s) and Fc epsilon receptors on lymphocytes

The IgE isotype-specific regulatory factor(s) of rodents as well as humans was shown to have an affinity to IgE molecules, suggesting that the factor(s) are Fc epsilon receptors (Fc epsilon R) on lymphocytes or include a fragment of Fc epsilon R. In order to test this possibility, the monoclonal anti-Fc epsilon R antibodies with different epitope specificities were prepared. FACS analysis showed that approximately 50 percent of B cells from normal individuals expressed Fc epsilon R and the augmentation of the expression was observed by the incubation with T cell factors and IgE. However, the Fc epsilon R expression on T cells was not detected even after induction. The result suggests that T cells may secrete Fc epsilon R but not express it on the surface or the IgE-binding factor(s) from T cells may not be antigenically cross-reactive with Fc epsilon R on B cells.     

Regulation of in vivo expression of Fc receptors for IgE (Fc epsilon R) on murine lymphocytes. II. Induction of Fc epsilon R and its inhibition in mice immunized with antigen

The induction of Fc receptors for IgE (Fc epsilon R) and its regulation were studied in BALB/c, SJL/J, and nude mice by a flow cytometric assay with the use of homologous monomeric IgE. Immunization of BALB/c mice with alum-absorbed antigen induced a remarkable increase in the expression of Fc epsilon R on spleen cells, whereas no enhancement of the Fc epsilon R expression was observed in SJL/J and nude mice after immunization. This increase was correlated with the elevation of serum IgE levels. However, the IgG antibody response, which is inducible even in SJL/J mice, was not associated with the induction of Fc epsilon R. The enhanced expression of Fc epsilon R in BALB/c mice observed in the primary or secondary IgE antibody response was detected in B cells with B220, surface IgM, and IgD, but not in T cells. The induction of Fc epsilon R in immunized BALB/c mice was inhibited by suppressive factor of allergy isolated from ascites fluids of SJL/J mice inoculated with complete Freund's adjuvant. In addition, both cyclophosphamide and prednisolone had an inhibitory effect on the induction of Fc epsilon R. These results suggest that the Fc epsilon R induction is inhibited not only by suppressive factor of allergy, which is effective in inhibiting the IgE antibody response selectively, but also by some immunosuppressive agents which are capable of suppressing all isotypes.     

Regulation of in vivo expression of Fc receptors for IgE (Fc epsilon R) on murine lymphocytes. I. Detection of Fc epsilon R+ lymphocytes by flow cytometry

Homologous monomeric IgE was employed in a flow cytometric assay for the detection of IgE Fc receptors (Fc epsilon R) on mouse lymphocytes. The expression of Fc epsilon R in normal BALB/c mice was detected on splenic and circulating lymphocytes, but not on bone marrow cells. The Fc epsilon R expression was observed in B cells with B220, surface IgM, and IgD, but not in T cells. Infection of mice with Nippostrongylus brasiliensis resulted in a marked increase in the expression of Fc epsilon R on splenic B cells. T cells, however, did not express Fc epsilon R even after N. brasiliensis infection. On the other hand, the Fc epsilon R expression on normal B cells decreased after a simple incubation at 37 degrees C for 24 h, while in the presence of IgE this decrease was inhibited. In contrast, B cells stimulated with interleukin 4 display Fc epsilon R with high densities. Interestingly, IgE enhanced the Fc epsilon R expression induced by interleukin 4, suggesting that both interleukin 4 and IgE may be responsible for an increase in the expression of Fc epsilon R on B cells of N. brasiliensis infected mice.