IgE Fc receptor positive T, B and NK cells in patients with the hyper-IgE syndrome

Patients with the hyper-IgE syndrome have greatly elevated percentages of IgE Fc receptor (Fc epsilon R)-positive B cells, but they have less than 0.1% Fc epsilon R+ T cells (T epsilon cells) and few, if any, Fc epsilon R+ natural killer cells. They also have markedly decreased numbers of IgG receptor positive (Fc gamma R+) T cells (T gamma cells). Patients with the hyper-IgE syndrome resemble in this respect patients with severe atopic dermatitis. Since a portion of T epsilon and T gamma cells of mildly atopic patients react with monoclonal antibody OKT8, they may have a suppressor function. However, whether the low number of T epsilon cells is responsible for the high IgE serum level in hyper-IgE syndrome and atopic dermatitis patients remains to be demonstrated. Attempts to obtain a reliable assay for human IgE synthesis in vitro to investigate the function of Fc epsilon R-positive lymphocytes proved to be difficult. Even isolated B cells from atopic donors seldom produced more than twice the quantity of IgE released from cells incubated in the presence of the protein synthesis inhibitor cycloheximide.     

The expression of IgE Fc receptors on peripheral blood monocytes in asthmatic patients]

We measured the expression of the IgE Fc receptor, Fc epsilon RII, on peripheral blood monocytes isolated from asthmatic patients and normal subjects by laser flow cytometry. After peripheral blood mononuclear cells were incubated with monoclonal antibodies, H107, which recognize Fc epsilon RII, FITC-labeled second antibodies were reacted with them. The cells were then incubated with PE-labeled Leu M3 monoclonal antibodies and the ratios of H107 positive monocytes were measured by two color analysis. The ratio of H107 positive monocytes in atopic asthmatic patients was significantly greater than the ratio in normal subjects. But the ratio was not higher in 9 out of the 14 atopic asthmatic patients. This indicated that atopic asthmatic patients are divided into two groups by the expression of Fc epsilon RII on monocytes. Total serum IgE level was not related to the ratio of H107 positive monocytes.     

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.     

The expression of IgE Fc receptors on lymphocytes of allergic patients

Peripheral blood lymphocytes from nonatopic subjects and atopic patients were analyzed for cells expressing Fc receptors for IgE (Fc epsilon R). Nonatopic humans and atopic patients in remission had approximately 1 percent of Fc epsilon R+ peripheral blood lymphocytes. Usually greater than 99 percent of these cells were mIgM+/mIgD+ B cells. However, in approximately 10 percent of nonatopic and atopic subjects a transient increase of Fc epsilon R+ lymphocytes to 3-6 percent was observed in the absence of any disease manifestations and measurable changes in the serum IgE level. At times of increased numbers of peripheral blood Fc epsilon R+ lymphocytes, up to 1 percent Fc epsilon R+ positive cells were detected in isolated T cell preparations. The Fc epsilon R+ T cells reacted with the monoclonal antibody Lyt 3 to the sheep erythrocyte receptor of human T cells but not the anti-T cell antibody OKT3, and fractions also with the monoclonal antibodies OKT8 (cytotoxic and suppressor T cells) and OKM1, which binds to an antigen present on monocytes and a subpopulation of T cells and large granular lymphocytes. No OKT4+ (helper T cells) Fc epsilon R+ cells were detected. The reactivity with monoclonal antibodies to T cell subsets of the Fc epsilon R+ T cells paralleled the reactivity of the IgG Fc receptor positive T cells. In contrast to patients with allergic rhinitis and asthma, patients with severe atopic dermatitis or the Hyper IgE Syndrome always had significantly elevated percentage of Fc epsilon R+ lymphocytes (4-10 percent), which were almost entirely B cells since less than 0.1 percent Fc epsilon R+ T cells were detected in these patients. Atopic dermatitis patients receiving systemic corticosteroid treatment had only 0.2 percent Fc epsilon R+ lymphocytes which was significantly less than the 1 percent of the nonatopic control donors. Attempts to define the function of Fc epsilon R on human B and T lymphocytes have been unsuccessful thus far; however, the increase of Fc epsilon R+ cells associated with atopic disease in man and parasitic infections in rats and mice suggest that Fc epsilon R+ lymphocyte may be involved in the IgE isotype regulation.     

Surface expression of Fc epsilon RI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis,allergic asthma,and rhinitis

BACKGROUND: Fc epsilon RI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell Fc epsilon RI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis. OBJECTIVE: We sought to investigate and localize Fc epsilon RI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases. METHODS: Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-Fc epsilon RI alpha (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-Fc epsilon RI alpha before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization. RESULTS: Cytoplasmic Fc epsilon RI alpha chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface Fc epsilon RI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface Fc epsilon RI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals. CONCLUSION: In clinically uninvolved skin, Langerhans' cell-surface Fc epsilon RI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions.     

Increase of T cells bearing Fc epsilon R-associated antigen in patients with atopic asthma

Subpopulations of peripheral blood mononuclear cells (PBMC) in patients with atopic asthma and control donors were analyzed by means of flow cytometry. T cells were isolated from PBMC by rosetting with sheep erythrocytes. The proportions of PBMC and T cells bearing receptors for Fc fragment of IgE (Fc epsilon R) were elevated in patients when determined with monoclonal antibody to Fc epsilon R-associated antigen (H107). Significant correlations were observed between the serum-IgE levels and proportions of Fc epsilon R+ T cells (r = .71, P greater than .002). In contrast, no differences were observed between the groups in the proportions of PBMC and T cells bearing receptors for Fc fragment of IgG (Fc8R) when measured with model IgG-immunocomplexes. The proportions of cells reacting with monoclonal anti-IgE (9G2), T11 (E receptor), Leu-2a (suppressor), Leu-3a (helper), Leu-4 (pan-T), Leu-12 (pan-B), and anti-polyvalent immunoglobulin did not differ significantly between the groups. The results indicate that Fc epsilon R+ T cells are increased in patients with atopic asthma, suggesting that these cells may be involved in the regulation and/or synthesis of IgE antibody formation in man.     

Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels.

BACKGROUND: It remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation. OBJECTIVE: We compared the number and function of mast cell progenitors present in the peripheral blood from donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis accompanied by high serum IgE (IgE > 5000 U/mL). METHODS: Purified peripheral blood cells were cultured in serum-free methylcellulose containing stem cell factor (SCF), IL-6 plus IL-3. Fresh methylcellulose containing the cytokines was layered over every 2 weeks. The cultured mast cells were retrieved from the methylcellulose and were functionally analysed. RESULTS: Mast cell colonies were distinguished at 6 weeks of culture as other colony types had been degenerated. The number of mast cell colony-forming cells varied depending on donors and was not significantly increased in peripheral blood from the hyper-IgE atopic patients. A significant inversed correlation was found between the number of mast cells per one colony and the ages of donors. The cultured mast cells derived from atopic patients and those from normal IgE donors equally expressed Fc epsilon RI and released histamine through Fc epsilon RI, although IL-4 priming in vitro markedly enhanced the function of mast cells regardless of donors. CONCLUSIONS: These results indicate that the number of circulating mast cell progenitors may be regulated by unknown individual factors unrelated to IgE levels. Mast cell function may be regulated largely by environmental factors, such as IL-4, but not determined by their progenitors' genotypes.     

Hyper-IgE and human immunodeficiency virus infection

A 39-year-old black male who is an intravenous drug abuser developed certain clinical manifestations that were consistent with the hyper-IgE syndrome. These included an extremely elevated IgE (greater than 2000 IU/mL), extensive eczematoid dermatitis, and recurrent soft tissue infections. He had no history of atopic disease as a child. Immunophenotypic analysis of peripheral blood mononuclear cells showed a significant decrease in helper (CD 4) cells with a normal concentration of suppressor (CD 8) cells. Human immunodeficiency virus (HIV) antibody was detected in his serum. Previous studies of patients with atopic dermatitis as well as of patients with the hyper-IgE syndrome characteristically show decreases in total suppressor lymphocyte concentrations in peripheral blood. These results led some investigators to postulate that high IgE concentrations in patients with atopic dermatitis result from defective IgE specific suppression. More recent evidence suggests that helper cell function may be the more critical impairment in these disorders. The development of a hyper-IgE syndrome in this setting of T-helper cell viral affliction lends further support to the hypothesis that helper lymphocyte defects may have a key role in the development of atopic dermatitis and the hyper-IgE syndrome.     

Secretion of IgE-specific potentiating factors by human Fc epsilon R+ T cell lines

In the present study, Fc epsilon R+ and Fc epsilon R- T cells were isolated from patients with the hyper-IgE syndrome and maintained in long-term cultures with interleukin 2. Supernatants from the Fc epsilon R+ but not from the Fc epsilon R- T cell lines enhanced IgE but not IgG synthesis in B cells derived from patients with allergic rhinitis. There was, however, no induction of IgE synthesis in B cells from nonatopic donors. The IgE-potentiating factors bound to IgE-Sepharose but not to IgG-Sepharose. The target B cells for these IgE binding factors appear to be preactivated IgE-bearing B cells.     

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.     

Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations.

Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkin's disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.     

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.     

Increased occurrence of IgE+ and FcεRI+ cells in adenoids from atopic children

BACKGROUND: To examine the influence of atopy on the different cell populations in adenoids, we investigated the presence of IgE+ cells, cells expressing the high-affinity receptor for IgE (Fc(epsilon)RI), and various other cell populations in adenoid tissue, in atopic and nonatopic children with otitis media with effusion (OME) or adenoid hyperplasia (AH). METHODS: Cryostat sections of adenoids from 14 atopic and 16 nonatopic children suffering from long-lasting OME (n=15) or obstructive AH (n=15) were investigated with immunohistochemical markers for T-cell subsets, mast cells, eosinophils, plasma cells, CD25, CD1a, IgE, and Fc(epsilon)RI. RESULTS: Sensitization to allergens was correlated to an increase of IgE+ cells in the epithelium (P<0.01), the extrafollicular area (P<0.0001), and the follicles (P<0.001) of the adenoids and an increase of Fc(epsilon)RI+ cells in the extrafollicular area (P<0.01). A minority of the IgE+ cells were plasma cells. No significant differences in cells stained for IgE, Fc(epsilon)RI, or the other markers were observed between patients with OME and AH. CONCLUSIONS: Atopy is associated with increased numbers of IgE+ and Fc(epsilon)RI+ cells in adenoids irrespective of whether the child has OME or AH.     

Immunoglobulin heavy chain patterns in reactive lymphadenopathy.

Thirty one lymph nodes taken from 24 benign reactive cases, three cases of angiolymphoid hyperplasia with eosinophilia, one case of Kimura's disease and three cases of Hodgkin's disease, were stained for immunoglobulin heavy chains IgG, IgM, IgA and IgE using the peroxidase-antiperoxidase method. Reticular staining of germinal centres and cells containing immunoglobulin in germinal centres and extrafollicular regions were features of all groups. No staining pattern was diagnostic for any of these conditions and in particular, the reticular staining pattern of IgE in the germinal centres that is frequently reported in Kimura's disease and in angiolymphoid hyperplasia with eosinophilia was non-specific.     

Lipoteichoic acid from Staphylococcus aureus enhances allergen-specific immunoglobulin E production in mice

BACKGROUND: Our previous study demonstrated that lipoteichoic acid (LTA) from Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously with an allergen. However, the effects of LTA on allergen-specific IgE production in such sensitized mice have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effects of LTA from S. aureus on allergen-specific IgE production in mice sensitized percutaneously with a house dust mite antigen (MA). METHODS: Mice were sensitized with a single topical application of MA and/or LTA to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE antibodies in sera from sensitized mice were detected by an enzyme-linked immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph nodes of sensitized mice were analysed by flow-cytometry (FACS). RESULTS: Simultaneous sensitization with MA and LTA increased IgE production 3 weeks later, significantly more than sensitization with MA alone. FACS analysis of CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen-presenting cells such as B lymphocytes and dendritic cells more than sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes showed that simultaneous sensitization with MA and LTA increased the number of CD40L-expressing Th cells more than sensitization with MA alone. CONCLUSION: These results suggest that LTA enhances allergen-specific IgE production by a mechanism associated with up-regulation of CD40L-expressing Th cells and this might explain the role of skin colonization with S. aureus in AD patients.     

Expression of Fc epsilon receptors and surface and cytoplasmic IgE on human fetal and adult lymphopoietic tissue

The appearance during ontogeny of IgE-positive and Fc epsilon receptor (FcER)-bearing cells was studied. Monoclonal antibody to the constant region (Fc) of IgE (CIA-E-7.12) was used to detect cytoplasmic and surface IgE. A monoclonal antibody to the low-affinity Fc epsilon receptor (FcER-II = CD23) and immune complexes composed of human IgE and mouse monoclonal anti-human IgE Fc were used to detect FcER. Cryostat sections of human fetal tissues (liver, lung, spleen, and thymus) from 11 to 22 weeks gestation as well as adult tonsil tissues were examined for IgE, FcER, and other lymphoid markers by immunoperoxidase staining. Although both IgE- and FcER-positive cells were present in adult tissues, we found that, in contrast to an earlier report, such cells were not present in the fetal tissues examined. The in situ location of FcER on cells in human lymphoid tissues revealed that the FcER-bearing cells were localized predominantly in the germinal centers (mature B cell and macrophage areas) of the tonsil follicles with some staining in the mantle (resting and less mature B cell areas).     

Quantification of indoleamine 2,3-dioxygenase gene induction in atopic and non-atopic monocytes after ligation of the high-affinity receptor for IgE,Fc(epsilon)RI and interferon-gamma stimulation

Antigen-presenting cells (APCs) are crucial in regulating the outcome of T cell responses. Certain APCs are able to down-regulate T cell proliferation in vitro by inducing the enzyme indoleamine 2,3-dioxygenase (IDO) upon interferon-gamma (IFN-gamma) stimulation. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. A lack of extracellular tryptophan creates environments in which cells become starved for this amino acid. The high-affinity receptor for IgE, Fc(epsilon)RI, is the principal receptor for the binding of specific IgE in type I-mediated allergies. We demonstrated recently that IDO is overexpressed in Fc(epsilon)RI-stimulated monocytes. In the present study, we performed quantification of IDO gene induction after treatment of atopic (Fc(epsilon)RI(high)) and non-atopic (Fc(epsilon)RI(low/-)) monocytes with IgE/anti-IgE and IFN-gamma. By quantitative PCR ELISA, we found IDO molecule induction in atopic monocytes was enhanced about 50-fold over non-atopic monocytes after ligation of Fc(epsilon)RI. Stimulation with IFN-gamma at a concentration of 100 U/ml in culture medium caused an increase in IDO gene copy numbers in atopics of about fourfold over that of non-atopics. This comparative quantification study demonstrates clearly the regulation of IDO gene expression by Fc(epsilon)RI and discloses differences thereof in atopic and non-atopic cells upon inflammatory stimuli.     

Isolation and characterization of IgE receptors from rat intestinal mucosal mast cells

High-(Fc epsilon RI) and low-(Fc epsilon RII) affinity IgE receptors were isolated from surface radioiodinated, Nonidet-P40-solubilized rat intestinal mucosal mast cells (IMMC) and compared with those on rat peritoneal mast cells (PMC) and rat basophilic leukemia (RBL) cells. Fc epsilon RII were isolated by affinity chromatography using IgE-Sepharose or by anti-Fc epsilon RII antisera and protein A-Sepharose. The surface-exposed, IgE-binding alpha subunits of Fc epsilon RI [Fc epsilon RI alpha] were isolated by affinity chromatography using IgE and anti-IgE-Sepharose. Fc epsilon RI alpha on IMMC had an apparent molecular mass of 59 kDa, somewhat larger than that of PMC (51 kDa), RBL-2H3 cells (51 kDa) or RBL-CA10.7 cells (46 kDa). Brief (45 s) incubation of IMMC or PMC in glycine-HCl, pH 3, prior to iodination removed much of the surface-bound IgE. This permitted more thorough labeling of the receptors, but had no affect on the estimate of receptor size. Surprisingly and in contrast to acid-treated PMC, upon anti-IgE-Sepharose isolation acid-treated IMMC yielded an intensely radioactive Fc epsilon RI alpha band in the absence of added IgE. Such a finding suggests that IMMC, more so than PMC, may have an intracellular store of IgE, as has been suggested by many others. IMMC also differed from PMC in the number of forms of Fc epsilon RII isolated; 50-kDa and 58-kDa forms of Fc epsilon RII were obtained from IMMC, whereas PMC yielded most often a single 56-kDa Fc epsilon RII band. These results were mimicked by the two RBL cell sublines: RBL-2H3 cells yielded two Fc epsilon RII (46 kDa and 55 kDa), but only one form of Fc epsilon RII (54-kDa) was obtained from RBL-CA10.7 cells. Thus, the two subtypes of rat mast cells, which have previously been shown to differ in mediator profile and responsiveness to secretagogues and antiallergic drugs, are also distinguished by differences in IgER profile.