Original Article

Journal of Investigative Dermatology (1990) 94, 15s–21s; doi:10.1111/1523-1747.ep12874984

Fc Receptors of Human Langerhans Cells

Didier A Schmitt1, Thomas Bieber2, Jean-Pierre Cazenave3 and Daniel Hanau1

  1. 1Laboratoire d'Histocompatibilité, Centre Regional de Transfusion Sanguine, Strasbourg, France
  2. 2Dermatologische Klinik und Poliklinik der Ludwig-Maximilians Universität, Münich, F.R.G.
  3. 3INSERM U.311, Centre Regional de Transfusion Sanguine, Strasbourg, France
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Abstract

Receptors for the Fc fragment of immunoglobulins (Fc R) exhibit specificities for a wide variety of immunoglobulin classes and subclasses. In humans, at least three distinct classes of receptors for the Fc fragments of IgG (Fcgamma RI, II, III) and two classes of receptors for the Fc fragments of IgE (Fcalt epsilon RI, II) have been characterized. These classes were largely defined on the basis of their affinities for different immunoglobulin subclasses and their reactivities with monoclonal anti-receptor antibodies. Among these FcR, in healthy individuals, epidermal Langerhans cells (LC) express only the Fcgamma RII/CDw32. This FcR – a member of the immunoglobulin superfamily – is only present on about 50% of freshly isolated CD1a positive cells, as determined by rosette assays. It has a Mr of 40 kDa, is trypsin resistant, binds polymeric human IgG and murine IgG 1-coated erythrocytes, and reacts with anti-CDw32 monoclonal antibodies (MoAb). LC internalize Fcgamma RII by receptor-mediated endocytosis. After 48 h of culture, human LC loose their Fcgamma RII, as revealed by flow cytometry. While the function(s) of the Fcgamma RII on human LC remain(s) unknown, this receptor may be primarily involved, like the Fcgamma RII present on mouse macrophages, in the clearance of extra-cellular immune complexes. In patients with atopic dermatitis having an elevated IgE serum level, beside an increased expression of the Fcgamma RII by LC located on lesional skin, IgE-bearing epidermal and dermal LC are present, again essentially on lesional skin. Double immunolabeling on cryosections reveals that on lesional skin only about 50% of the epidermal CD1a positive cells bear IgE. This capacity of LC to bind IgE molecules appears to be due to the presence of a specific Fcalt epsilon R. While the class of this Fcalt epsilon R still remains unclear, it appears to have some particularities: i) an associated expression with the CD 1 a antigen, ii) an affinity for IgG, and iii) a trypsin resistance. In vitro, human recombinant interleukin (IL)-4 and/or interferon (IFN)-gamma are able to induce the synthesis and expression of Fcalt epsilon RII/ CD23 on a percentage of normal human epidermal LC. This Fcalt epsilon RII seems to be functional since it binds IgE molecules, this binding being prevented by preincubation with anti-CD23 MoAb. The expression of Fcalt epsilon RII/CD23 by LC in vitro is accompanied by the release of IgE-binding factors (BF). Addition of human recombinant IL-1, IL-3, and IL-6 decreases the IL-4/IFN-gamma-induced CD23 expression on LC. These data suggest that T-cell derived cytokines (IL-4, IFN-gamma) may induce the Fcalt epsilon RII/CD23 expression on normal human LC, while keratinocyte-derived cytokines (IL-1,3,6) may have a regulatory role in this phenomenon. Fcalt epsilon RII/ CD23-positive LC may play a major part in the pathogenesis of atopic eczema and, by the release of IgE-BF, in the regulation of IgE synthesis.

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