IgE Antibody Synthesis Research Articles

Quality of life of patients undergoing specific allergen immunotherapy in allergic rhinitis

Although allergic diseases have been known since antiquity, both their understanding and systematics came later. The World Allergy Organization (WAO) defines the phenomenon of atopy as a predisposition of a person or family to the uncontrolled synthesis and release of IgE antibodies. Allergic rhinitis (AR) is one of the most important clinical diseases of rhinitis (NN, rhinitis). AR significantly reduces the quality of life, tends to increase, and its consequences may be life-threatening diseases. The aim of the study is to determine the quality of life of patients who underwent specific allergen immunotherapy in allergic rhinitis. The study was conducted at the Center for Specialist Allergology in Lublin between October 2018 - February 2019. The study covered a group of 157 patients. The diagnostic method used was a questionnaire. The first research tool was own questionnaire consisting of 31 questions. The second tool was the standardized questionnaire, the Polish version of the SF-36 Quality of Life Questionnaire. Studies have shown statistically significant changes in the symptoms of before and after immunotherapy, which means improving the quality of life and reducing the severity of symptoms and problems of respondents after therapy. The respondents were not in the best of health (50%). Over 50% of respondents said that the immunotherapy process significantly reduced personal / family expenses for treatment associated with allergic rhinitis. The conducted process of specific allergen immunotherapy improved the quality of life of respondents by increasing awareness of the quality of life through the prism of health change in relation to the general indicator in the area of mental problems by reducing their nuisance value more than in the area of somatic symptoms.

Effect of a cocoa-enriched diet on immune response and anaphylaxis in a food allergy model in Brown Norway rats

Previous studies have demonstrated that cocoa intake decreased Th2 immune-related antibodies in rats. In consequence, we aimed to study in depth this cocoa action, particularly assessing its effect on a rat model of food allergy (FA) and also on an anaphylactic response. The involvement of the intestinal immune system was analyzed to allow the action mechanisms to be investigated. The role of cocoa flavonoids in the antiallergic properties of cocoa was also established. Brown Norway rats were fed either a reference diet or diets containing conventional cocoa (CC) or nonfermented cocoa (NFC). FA to ovalbumin (OVA) was induced and, later, an anaphylactic response was provoked. As expected, the synthesis of anti-OVA IgE and other Th2-related antibodies was inhibited by CC diet. In addition, the release of mast cell protease II after anaphylaxis was partially prevented by CC, although other variables were not modified. The CC diet also attenuated the increase of some Th2-related cytokines released from mesenteric lymph node and spleen cells, and modulated the intestinal gene expression of molecules involved in allergic response. These results demonstrated the local and systemic influence of CC diet. The effects of the NFC diet were weaker than those of CC, suggesting that cocoa components other than flavonoids play a role in cocoa's action. In conclusion, by acting on intestinal and systemic immune functions, a cocoa-enriched diet in rats exhibited a protective effect against FA and partially against anaphylaxis, making this a food of high interest to the fields of health and immunonutrition.

Detection of auto-anti-idiotypic antibodies toLol p I(rye I) IgE antibodies in human sera by the use of murine idiotypes: levels in atopic and non-atopic subjects and effects of immunotherapy

Anti-idiotypic antibodies (anti-Id Abs) are involved in the regulation of a number of immune responses including the IgE antibody production. In atopic patients, the increased synthesis of IgE antibodies could be related to a defective production of regulatory anti-Id Abs. In the present study, we first developed a sensitive assay for measuring the levels of anti-Id Abs directed against antibodies specific for Lol p I, the major allergenic determinant of Lolium perenne (rye grass). In this assay, we used previously described murine monoclonal anti-Lol p I antibodies that were shown to share epitopic specificities with human anti-Lol p I IgE and IgG antibodies, thus short-cutting the need for purification of F(ab')2 fragments of human IgG Abs and insuring optimal specificity and sensitivity. Levels of anti-Id Abs against two anti-Lol p I monoclonal antibodies (290A-167, 348A-6) were higher in normal volunteers than in untreated atopic patients. Specific immunotherapy increased the levels of anti-Id Abs to those of normal volunteers. These observations suggest a role for the Id-anti-Id network in the regulation of IgE antibody production.

Mechanisms in adverse reactions to foods: a review

Human diet consists of an enormous variety of both plants and animal proteins, many of which are potentially immunogenic. Industrial processing of foods and digestion in the gastrointestinal tract causes changes and breakdown of proteins into peptides, which are also potential immunogens. Foods commonly known to cause allergic reactions are fish, milk, eggs, fruits, vegetables, nuts, legumes and meat. Once sensitised to a particular antigen, subsequent exposure may result in a marked and immediate reaction characterised by vomiting, diarrhoea, abdominal cramps, itching and swelling of the mouth and skin, dizziness and occasionally systemic anaphylaxis. Allergic reactions involve complex processes and interactions between the allergen and immunological components in the digestive tract such as antigen absorption, processing and presentation, T cell and B cell activation, development of oral tolerance or allergic sensitivity, antigen‐specific IgE antibody synthesis. Allergen binding to allergen‐specific mast cell membrane‐bound IgE antibodies triggers mast cell degranulation. This results in the release of histamine and other chemotactic mediators responsible for clinical symptoms.

Reduced Interferon-γ Production and Mutations of the Interleukin-12 Receptor β2 Chain Gene in Atopic Subjects

Background: The atopic patient has a predisposition to selective synthesis of IgE antibodies to common environmental antigens. IgE production is upregulated by interleukin-4 (IL-4) and downregulated by interferon-γ (IFN-γ). IL-12 is a cytokine that induces IFN-γ production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. Methods: We examined IFN-γ production in peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients. Moreover, sequences of the IL-12R β₂ chain gene were analyzed. Results: The serum IgE levels were negatively correlated (p < 0.001) with IFN-γ production. In 24 out of 75 atopic patients, IFN-γ production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-γ production. Sequence analysis of the cDNA of IL-12R β₂ revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-γ production following IL-12 stimulation was under the detection limit. PBMCs cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine phosphorylation of Stat4. Conclusions: The results of our study indicate that atopic diseases are caused, in part, by impairment of the IL-12 signal cascade, which downregulates IgE production, and that the mutation of the IL-12R β₂ chain gene is one of the causative genes for atopy.

Mechanisms of allergen-specific immunotherapy.

Mechanisms of allergen-specific immunotherapy.

Redirecting Th2 responses in allergy.

Atopic diseases are genetically determined disorders which affect approximately 20%–30% of the general population in developed countries and whose prevalence is increasing over the last decades. They are characterized by an enhanced ability of B lymphocytes to produce IgE antibodies in response to certain groups of otherwise innocuous environmental antigens that can activate the immune system after inhalation or ingestion, and perhaps after penetration through the skin (allergens). Allergen-specific IgE antibodies bind indeed to high affinity (type I) Fce receptors (FceRI) present on the surface of mast cells/basophils and allergen-induced FceRI cross-linking results in the release of vasoactive mediators, chemotactic factors and cytokines that in turn trigger the “allergic cascade” (Lichtenstein 1993). In addition to IgE-producing B cells and IgE-binding mast cells/basophils, eosinophils are also involved in the pathogenesis of atopic diseases, inasmuch as these cells accumulate in the sites of allergic inflammation and the toxic products they release significantly contribute to the induction of tissue damage (Gleich et al. 1994). In the past few years, the cellular basis for the regulation of IgE antibody production has been discovered. More importantly, the intense study on the functional properties of helper T (Th) cells that collaborate with B cells for the synthesis of IgE antibodies has allowed clarification of the mechanisms accounting for the joint involvement of IgE-producing B cells, mast cells/basophils and eosinophils.

Unique profile of IL-4 and IFN-γ production by peripheral blood mononuclear cells in infants with atopic dermatitis

Although the level of house dust mite (HDM)–specific lymphocyte proliferation is high in infants with atopic dermatitis (AD), the level of HDM-specific IgE antibody (HDM-IgE-RAST) is usually very low or negative. To elucidate the cause of the deficient HDM-specific IgE antibody formation in infants with AD, we examined the profile of IL-4 and IFN-γ production by HDM-stimulated PBMCs. The amount of IL-4 production was higher in infants with AD and in children with AD (3 to 15 years) than in the nonatopic control subjects. Although the amount of IFN-γ production in children with AD was lower than that found in nonatopic children, it was higher in infants with AD than in nonatopic infants. This result suggests that HDM-specific helper T lymphocytes in infants with AD have not yet differentiated into T H2 but rather stayed at the stage of T H0. The level of IgE-RAST for egg white (EW) is already elevated in infants with AD. The amount of IL-4 produced by EW-stimulated PBMCs was comparable to that produced by HDM-stimulated PBMCs in infants with AD. However, the amount of IFN-γ produced by EW-stimulated PBMCs was distinctly lower than that produced by HDM-stimulated PBMCs in infants with AD. Although there was no correlation between the amount of IL-4 production by HDM-stimulated PBMCs and the level of HDM-IgE-RAST in infants with AD, the amount of IL-4 production by EW-stimulated PBMCs was closely correlated with the level of EW-IgE-RAST. These results suggest that it is not the lack of IL-4 but rather a relative increase in IFN-γ production by HDM-specific helper T lymphocytes that causes the deficiency of HDM-specific IgE-antibody synthesis in infants with AD. (J Allergy Clin Immunol 1998;102:238-44.)

ANTIALLERGIC/ANTIASTHMATIC ACTIVITY OF OLIGOPEPTIDE RELATED TO IgE

In spite of continuous research in the field of bronchial asthma, still no satisfactory drug is available. Recently a new class of oligopeptide exhibited antiallergic activity by inhibiting the synthesis of IgE antibody. The analogue of ADSDGK (94-335) has shown antiallergic activity in experimental models. The 94-335 inhibited the passive cutaneous anaphylaxis (PCA) reactions in rats in a dose-dependent manner (0.5–10 mg kg−1p.o.) by 47–90%. There was a 70–87% protection of mast cell degranulation induced by compound 48/80 with peptide 94-335 at 0.5–1.5 mg kg−1p.o. in rats. This peptide also inhibited antigen- induced contraction in sensitised guinea pig ileum. There was 18 and 72% protection to bronchoconstriction induced by histamine and egg albumin, respectively, in an aerosol test in guinea pigs. These effects of compound 94-335 were comparable with that of the clinically-used antiallergic drug disodium cromoglycate (DSCG). The results suggest that peptide 94-335 possesses potent antiallergic activity.

Selective type-1 hypersensitivity to cefuroxime

J Allergy Clin Immunol 1998;101:564-5.

T-cell receptor Vβ gene segment expression in diisocyanate-induced occupational asthma

Background: Diisocyanates are the most common cause of occupational asthma induced by low-molecular-weight chemicals. The disease appears to be immunologically mediated but is independent of IgE antibody synthesis. An underlying genetic susceptibility is suggested by the fact that the disease only develops in approximately 5% to 10% of exposed workers. Objective: The study was designed to determine whether disease susceptibility is influenced by HLA and T-cell receptor Vβ gene segment usage. Methods: T-cell receptor Vβ gene repertoires were quantitated by using primer pairs specific for Vβ gene segments in conjunction with a common Cβ region primer. One group of workers with diisocyanate-induced occupational asthma produced diisocyanate-specific IgG and IgE antibodies, whereas the other group did not produce specific antibodies. Occupational asthma was previously confirmed by either workplace challenge or laboratory specific diisocyanate bronchoprovocation. Control groups consisted of diisocyanate-exposed workers who were free of symptoms, patients with nonoccupational asthma, and unexposed subjects who were free of symptoms. Results: Lymphocytes from workers with diisocyanate-induced occupational asthma had significantly decreased Vβ1 and Vβ5 gene segment expression before in vitro exposure to diisocyanates, compared with control groups. Percent Vβ1 and Vβ5 gene segment expression was selectively increased when peripheral blood mononuclear cells were stimulated in vitro with diisocyanate-conjugated proteins. Low-resolution HLA class II phenotyping revealed no significant differences in the distribution of HLA-DR or HLA-DQ alleles between diisocyanate-induced occupational asthma and control groups. Conclusions: These findings are consistent with a hypothesis that antigen-specific T-cell subpopulations may be sequestered in the lungs of workers with diisocyanate-induced occupational asthma and clonally expand after further exposure to diisocyanates. (J Allergy Clin Immunol 1997;99:245-50.)

Potential allergens stimulate the release of mediators of the allergic response from cells of mast cell lineage in the absence of sensitization with antigen-specific IgE.

A number of structurally diverse antigens preferentially stimulate the synthesis of IgE antibodies, but no unifying principle has been proposed that explains the nature of isotype selection. In the present study, we show that common allergens present in bee venom, house dust mite emanations and parasite proteins induce mast cell and basophil degranulation and stimulate interleukin-4 synthesis, and secretion in the absence of antigen-specific IgE. These data point to a linkage between the initial activation of cells of the innate immune system and subsequent adaptive immune responses. They suggest that IgE-independent mast cell and basophil degranulation is predictive of potential allergenicity and can be evaluated by means of a cellular assay. Our study indicates that non-immunological degranulation by prototypic allergens, such as bee venom phospholipase A2 or proteases associated with house dust mite emanations, is critically dependent on enzymatic activity. These findings have potentially important implications for vaccine design in allergic and parasitic disease.

Characterization of histamine releasing factors in diisocyanate-induced occupational asthma

Immunologic mechanisms contributing to diisocyanate-induced occupational asthma (OA) are poorly defined. There is a relatively low incidence of diisocyanate-specific IgE antibody responses. The frequent occurrence of delayed onset asthmatic responses in workers with diisocyanate asthma suggests a role for cellular immune mechanisms. We have shown in vitro production of antigen-specific mononuclear cell-derived histamine releasing factors (HRF) by peripheral blood mononuclear cells (PBMCs) of workers with OA. Monocyte chemoattractant protein-1 (MCP-1) and RANTES (acronym for “regulated on activation normal T expressed and secreted”) are chemokines found in PBMC supernatants that express HRF activity. Diisocyanate-exposed workers were tested for diisocyanate antigen-stimulated enhancement of HRF, MCP-1, and RANTES production in supernatants of PBMCs and for serum specific IgE and IgG antibody levels to diisocyanate antigens bound to human serum albumin (HSA). PBMCs of workers with diisocyanate OA showed significantly increased production of antigen-specific HRF activity and MCP-1 ( >300 ng/ml) compared to diisocyanate-exposed asymptomatic workers ( P < 0.05). Antigen-stimulated enhancement of MCP-1 mRNA was demonstrated by reverse-transcription PCR. RANTES mRNA and chemokine secretion (< 1 ng/ ml) was also demonstrated in PBMCs, but did not show antigen enhancement in OA workers. Hapten specificity for the diisocyanate chemical to which a patient had been exposed was demonstrated for HRF enhancement and for IgG antibody reactions, but not for IgE reactions. HRF production was demonstrated in PBMC subpopulations, including lymphocytes and purified T cells. OA subjects showed increased CD8 + cells by immunofluorescence (mean CD4 +:CD8 + = 1.2 ± 0.2). The results suggest that diisocyanate antigen enhancement of HRF and MCP-1 production are stimulated by hapten-specific T cell reactions. Since a weak association has been found between IgE antibody synthesis and induction of diisocyanate OA, the role of T cell cytokines and chemokines in the pathogenesis of OA requires further investigation.

Prolonged inhibition of IgE production in mice following treatment with an IgE-specific immunotoxin

The synthesis of IgE antibodies by B cells is the first in a series of steps resulting in an allergic response. To eliminate IgE-bearing B cells and thereby prevent IgE production, we have developed an immunotoxin (ITA) composed of the non-anaphylactic 84.1c anti-mouse IgE mAb and the A chain of ricin (ricin A). This ITA specifically inhibited the induction of IgE synthesis by lipopolysaccharide plus interleukin-4 (LPS+IL-4) in vitro, and antigen-specific IgE production in vivo in adult mice. A single dose of anti-IgE ITA, given within a week (either before or after) of antigen challenge completely abolished antigen-specific primary IgE responses. No IgE production was seen for 2 months after ITA treatment. Following antigenic re-challenge, a suppressed secondary response (over 50% reduction) was still seen in the ITA-treated mice, 100 days after immunization. The results of this study demonstrate the potential use of anti-IgE toxin conjugates for the suppression of periodic (seasonal) allergic outbreaks.

Administration of IL-12 during ongoing immune responses fails to permanently suppress and can even enhance the synthesis of antigen-specific IgE.

The synthesis of antibodies of the IgE isotype in mice largely depends on IL-4, a cytokine that is released by T lymphocytes of the Th2 subtype. IL-12 is a cytokine considered to direct Th cell development into a Th1 direction and to suppress Th2 responses including the synthesis of IgE. Here we report about the influence of IL-12 on the IgE responses of mice immunized with protein antigens adsorbed to aluminum hydroxide. To avoid problems with the detection of IgE caused by an excess of competitive IgG antibodies produced in IL-12-treated mice, serum IgE was first extracted from the serum by plate-bound anti-IgE mAb and then determined either as total IgE or as antigen-specific IgE by using biotinylated anti-IgE or biotinylated antigen. Depending on the strain of mice and the dose of IL-12 injected together with the antigen, IL-12 can either temporarily suppress or augment the synthesis of (antigen-specific) IgE antibodies. This applies for CBA/J mice immunized six times in biweekly intervals with minute (0.1 micrograms/injection) or three-times with large (5 micrograms/injection) amounts of the bee venom allergen phospholipase A2 (PLA2). Under both conditions the antibody response is characterized by the production of predominantly IgG1 as well as IgE but very little IgG2a, IgG2b and IgG3 antibodies. Simultaneous application of low doses of IL-12 (1 or 10 ng/day) led to a 2- to 4-fold enhancement of IgE production (PLA2-specific IgE or total IgE). Only a high dose of 1 micrograms IL-12/day resulted in a 3- to 10-fold reduction of the IgE response. This suppression was not stable, however, because the synthesis of IgE antibodies was stimulated to a high level when these mice subsequently received a second course of immunizations in the absence of IL-12. Likewise, the synthesis of IgE was only temporarily suppressed by IL-12 treatment in CBA/J mice immunized with keyhole limpet hemocyanin (KLH) as antigen. However, application of low (10 ng/day) or high (1 microgram/day) doses of IL-12 during the primary course of immunizations of CBA/J mice with KLH suppressed the IgE response slightly or strongly respectively. In striking contrast, the KLH-specific IgE response of BALB/c mice was upregulated even when high doses of IL-12 (1 microgram/day) were injected simultaneously with the immunizations. Thus, these results demonstrate a great variability regarding the influence of IL-12 treatment on ongoing IgE responses in vivo.

Effects of IL‐4 and IL‐13 on total and allergen specific IgE production by cultured PBMC from allergic patients determined with recombinant pollen allergens

Interleukin (IL)-4 and IL-13 have been shown to be potent switch factors for IgE synthesis in human B cells. In this study we investigated the effects of recombinant human IL-4 and IL-13 on total and allergen specific IgE synthesis by peripheral blood mononuclear cells (PBMC) from pollen allergic patients and healthy control individuals. Peripheral blood mononuclear cells (PBMC) from allergic patients were investigated for their capacity to produce allergen specific IgE in vitro. Total protein extracts from birch pollen and timothy grass pollen as well as purified recombinant birch pollen allergens, Bet v I, birch profilin (Bet v II) and recombinant timothy grass pollen allergens, Phl p I, Phl p II, and Phl p V were used to measure specific IgE-antibody synthesis in cell culture supernatants by IgE-immunoblot and ELISA. PBMC obtained from allergic patients spontaneously secreted allergen specific IgE in the culture supernatants. Addition of Interleukin 4, Interleukin 13 and anti-CD40 antibody to the cultures alone or in combinations significantly induced total IgE production whereas allergen specific IgE production was not affected. Our results indicate that the peripheral blood of allergic individuals contains long lived allergen specific B cells which have already switched to IgE production and which are not sensitive to IL-4 and IL-13 treatment. These results may have implications on attempts to use cytokines or cytokine antagonists in therapy of Type I allergy.

Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum

It is well known that helminthic infection can cause a polyclonal stimulation of the synthesis of IgE, which is dependent on interleukin-4 (IL-4) production, and it has been suggested that this can modulate the expression of allergic reactivity in tropical populations. We evaluated the effect of regular anthelmintic treatment, for a period of 22 months, on certain aspects of the allergic reactivity of children in a slum area of Caracas, Venezuela, where helminths are endemic. The treatment (Oxantel-Pyrantel; Quantrel) effectively eliminated intestinal helminthic infection and resulted in a significant decrease in the initially elevated total serum IgE levels. IL-4 was detectable in the serum, and a significant reduction in IL-4 was also observed after treatment. In contrast, both the immediate-hypersensitivity skin-test reactivity and serum levels of specific IgE antibody against environmental allergens were markedly increased in the treated children. In a group of children who were also evaluated in the same slum, but who declined treatment, a substantial increase in helminthic infection occurred, which was related to an acute deterioration of the socioeconomic conditions of Venezuela over the course of our study period. This was paralleled by a considerable increase in total IgE levels in these children and a decrease in the skin-test reactivities and specific IgE levels. The application of Prausnitz-Küstner passive transfer tests and analysis of specific IgE antibody levels indicated that the pofyclonal stimulation of IgE synthesis by helminthic parasites results in mast cell Fcϵ receptor saturation and suppression of specific IgE antibody synthesis. This inhibition of allergic reactivity is reversible by anthelmintic treatment.

Interleukin-3-treated non-B, non-T cells switch activated B cells to IgG1/IgE synthesis.

The switch of activated B cells to IgE synthesis is an interleukin (IL)-3-dependent process. It is currently thought that specific T cells activated by antigen presented in the context of class II major histocompatibility complex are the major source of IL-4. Recently it has been demonstrated that a splenic non-T non-B cell population (termed NBNT) has the capacity to produce IL-4 following IgE and IgG receptor cross-linkage. In this study we demonstrate that IL-4 producing NBNT cells can induce the switch of lipopolysaccharide-activated B cells to the synthesis of IgG1 and IgE antibodies. Furthermore, it was found that not only IgE receptor cross-linkage but IL-3 was able to stimulate NBNT cells to produce IL-4 and induce the switch of B cells to IgE synthesis. NBNT cells derived from the spleen and bone marrow of SCID mice were able to produce IL-4 on exposure to IL-3. This suggested that the ability of IL-3 to stimulate IL-4 production was not dependent on prior exposure of the NBNT cells to antibody complexes in vivo. Taken together these findings represent the first observation that enough IL-4 is produced by NBNT cells to actually influence a B cell IgG/Ig response. The findings also clearly demonstrate that B cells do not need high concentrations of IL-4 to be directed to switch to IgG1 and IgE synthesis.

Elicitation of antigen-induced primary and secondary murine IgE antibody responses in vitro

Described herein are methods for eliciting and quantitating primary and secondary murine IgE antibody responses in vitro, and the important role of antigen concentration in determining the level of IgE produced during an immune response. The methods for quantitating IgE antibody levels in culture supernatant fluids and in serum by ELISA are presented in detail. The specificity of such methods was confirmed in that (1) no other isotype of antibody registered in the IgE-ELISA, and (2) parallel determinations of IgE antibody concentrations could be obtained by independent analysis using FcϵRI-dependent basophil degranulation. We examined various parameters of cell donor immunization and lymphoid cell culture which allow for optimal in vitro primary and secondary IgE responses. High relative antigen doses result in diminished IgE antibody responses in experimental animals, a finding confirmed herein. High antigen concentrations in vitro also result in relative suppression of IgE antibody synthesis. This was also true for in vitro production of IgG1 and IgA antibodies. Conversely, IgM and IgG2a responses were elicited at both low and high antigen concentrations; IgG2b and IgG3 were not produced under the conditions of priming and culture used herein. Finally, production of IgE in vitro depended on the presence of carrier-primed CD4 + T cells and hapten-specific B cells. Generation of maximal IgE antibody secretion, and hence elicitation of an allergic reaction, is thus dependent on the amount of antigen acting as stimulant for the immune response.

Purification of murine suppressive factor of allergy into distinct CD23-modulating and IgE-suppressive proteins.

The murine suppressive factor of allergy (SFA) has been purified from a T-cell hybridoma and found to consist of two functionally and biochemically distinct protein molecules. One protein (17 kDa) modulates the low-affinity Fc receptor for IgE on lymphocytes (i.e., CD23); it decreases the binding avidity of IgE to CD23-bearing B cells without affecting quantitative expression of CD23 and is thus designated epsilon-receptor-modulating protein. The second protein (30 kDa) suppresses IgE biosynthesis (i.e., SFA). This purified SFA suppresses interleukin 4-induced IgE and IgG1 synthesis by lipopolysaccharide-activated spleen cells but has no effect on other antibody isotypes; since the activity of SFA is not blocked by anti-interferon gamma monoclonal antibody, it is thus distinct from interferon gamma. The data presented indicate that epsilon-receptor-modulating protein and SFA are protein molecules that are involved in modulating the CD23 molecule and IgE antibody synthesis, respectively.