[Immunoglobulins E and inflammatory cells]. / Immunoglobulines E et cellules de l'inflammation.

Immunoglobulins E (IgE) have a privileged relationship with inflammatory cells due to the fact that there are different receptors for their Fc fragment expressed on the cell's surface. Currently one recognises at least three types of receptor: high affinity receptors (Fc epsilon RI) which are present on the surface of mast cells, basophils, and Langerhans cells. The receptors of low affinity (Fc epsilon RII) are represented on the surface of numerous inflammatory cells (eosinophils, lymphocytes, platelets...) and some lectine type (epsilon BP) receptors which are present on polymorpho-nuclear neutrophils and activated macrophages. The IgE interaction in the presence of specific antigens on the receptor may lead to cellular activation by transduction mechanism which are becoming better understood. This sequence of events, combined with the mechanisms of immediate hypersensitivity lead to the liberation of mediators and cytokines which nature varies according to the cell type and its environment. Polymorpho-nuclear eosinophils, mast cells, basophils and many other cells comply with this type of activation. However, the relationship between IgE and cells is not limited to this type of activation response. In the absence of specific antigen, IgE may sometimes play an inhibitory role on cellular functions; it is the case of blood platelets and polymorpho-nuclear neutrophils. Finally, IgE also participates in normal mechanisms of immune defence and may perhaps, by their presence on the surface of the dentritic cells, be determining factors in the function of antigen presentation. The diversity of IgE action at cellular level may equally be observed at the level of the bronchus, on organ which is implicated in allergic pathology. Passive sensitisation of the human bronchus by IgE may have at least two types of effect on the contractile response observed in vivo: in the presence of specific antigen it enables the contraction of bronchial smooth muscles and in the absence of antigen it could change the contractile response to non-specific agonists as it is observed in vivo in bronchial hyper-reactivity.

Functional characterization of the signal transduction events mediated by Fc epsilon RI alpha and gamma chimeric receptors.

Chimeric receptors containing the Fc epsilon RI alpha and gamma subunit domains were constructed, stably transfected into RBL-2H3 cells, and characterized for the biochemical events which are elicited upon receptor aggregation. Chimeric receptors containing the extracellular (EC) domain of the human Fc epsilon RI alpha subunit, or the EC domain of the p55 subunit of the interleukin-2 receptor were fused to the human Fc epsilon RI gamma subunit transmembrane and cytoplasmic (CT) domains or only the CT domain. The chimeras generated included alpha/gamma/gamma, I/gamma/gamma, alpha/I/gamma or I/I/gamma. The results indicate that both the Fc epsilon RI alpha EC domain and the Fc epsilon RI alpha CT domain are essential for signalling.

Mechanisms of the human allergic response. Clinical implications.

During the past decade, there have been enormous strides made in our understanding of the mechanisms underlying the human allergic response. In particular, interleukin-4 and interleukin-5 play a critical role in this process. This article details the understanding of the mechanisms underlying the regulation of allergic response, which is critical to the development of new treatment of allergic diseases.

A 2.8 Mb YAC contig in 11q12-q13 localizes candidate genes for atopy: Fc epsilon RI beta and CD20.

An important locus for Atopy (familial asthma, hay fever and eczema) has been localized to the 11q12-q13 region with the minimum recombination fraction around the CD20 gene. We have constructed a 2.8 megabase (Mb) Yeast Artificial Chromosome (YAC) contig of the candidate region using 15 STSs. A total of seven genes have been mapped within this interval in the order cen-OSBP-TCN1-GIF-Fc epsilon RI beta-CD20-CD5-PGA-q(ter) and can be covered by a minimum of eight YAC clones. Contig integrity was assayed with fluorescence in-situ hybridization (FISH) and the mapping of YAC ends on somatic cell and radiation hybrid panels. A long range restriction map of the contig has been constructed to establish the order of and distance between loci. Two promising candidates for the atopy locus, the beta subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI beta) and CD20, a molecule involved in B cell differentiation, have been placed within the contig.

Anti-human IgE monoclonal antibodies recognizing epitopes related to the binding sites of high and low affinity IgE receptors.

Anti-human IgE monoclonal antibodies (mAbs) were produced and eight clones recognizing epitopes on native IgE were selected. Epitopes were mapped by a competitive inhibition enzyme-linked immunosorbent assay, Western blotting and a multi-pin peptide technology. Four sites (one each in the C epsilon 1, C epsilon 2, C epsilon 2/C epsilon 3 junction and C epsilon 3) were recognized by the mAbs. The relationship between the four epitopes and the binding sites of high and low affinity IgE receptors (Fc epsilon RI and Fc epsilon RII, respectively) was studied using a monovalent Fab fragment of each mAb as a binding inhibitor. The IgE-Fc epsilon RII binding was clearly inhibited by the mAb recognizing the C epsilon 2/C epsilon 3 junction, suggesting that Fc epsilon RII binds to a rather limited area around the C epsilon 2/C epsilon 3 junction. The IgE-Fc epsilon RI binding, on the other hand, was scarcely inhibited by any single mAb. However, the binding was inhibited when the epitope in C epsilon 2 was blocked simultaneously with that at the C epsilon 2/C epsilon 3 junction or with that in C epsilon 3, indicating that these three distinct epitopes are related to the Fc epsilon RI binding sites. When these three epitopes were shown in the stereograph of human IgE, the Fc epsilon RI binding area was spread largely on the groove side between C epsilon 2 and C epsilon 3 domains. These results suggest that Fc epsilon RI acquires the high affinity through multiple bindings.

Demonstration of the high-affinity IgE receptor (Fc epsilon RI) on Langerhans cells of oral mucosa.

Langerhans cells in the skin have recently been shown to bind IgE molecules via a high-affinity IgE receptor. Using two specific antibodies, 29C6 and 6F7, against the alpha-chain of the high-affinity IgE receptor, we here demonstrate that Langerhans cells express this receptor in oral mucosa. A specific antibody, Tü1, against the low-affinity IgE receptor showed only low expression of this receptor. High-affinity binding for IgE may be important for induction and support of Langerhans cell-dependent transepithelial IgE-mediated allergic reactions and inflammation.

[Correlational study between lymphocyte IgE markers: membrane CD23 (mCD23) and soluble CD23 (sCD23) in an atopic population]. / Etude corrélative entre les marqueurs lymphocytaires de l'IgE:CD23 membranaire (mCD23) et CD23 soluble (sCD23) dans une population atopique.

IgE has two types of receptors: high affinity RFc sigma I and low affinity RFc sigma II. The latter may be studied by flow cytometry by the membrane marker CD23 (mCD23), expressed on B and T cells, monocytes, macrophages, Langerhans cells, eosinophils and platelets. Soluble CD23 (sCD23) corresponds with the extracellular C terminal domain of mCD23. The aim of the study was to search for a correlation between the levels of mCD23 and sCD23, comparatively with IgE, eosinophils, eosinophil cationic protein (ECP) and to the cytokines IL2, IL4 and IL6. 78 patients took part in the study, divided into two groups: Group 1 = atopics (n = 61); Group 2 = controls (n = 17). The majority presented with rhinitis, asthma, atopic dermatitis isolated or associated. The results showed a highly significant correlation between mCD23 and sCD23 compared with the control group. There was also a statistically significant increase for mCD23, sCD23, cytokines IL2, IL4 and IL6, mediator ECP in parallel with eosinophils and total IgE. This study confirms amongst other things the rise in IL4 in atopy and the correlation between the level of ECP and that of eosinophils, and that there is an overall correlation between mCD23 and sCD23.