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Eur Respir J Suppl. 1996 Aug;22:63s-66s.

Pairs of surface molecules involved in human IgE regulation: CD23-CD21 and CD40-CD40L.

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1
Glaxo Institute for Molecular Biology, Planles-Ouates,Geneva, Switzerland.

Abstract

At least two cell-derived signals have been shown to be necessary for the induction of immunoglobulin isotype switching in B-cells. The first signal is given by either of the soluble lymphokines, interleukin (IL)-4 or IL-13, which induce germline epsilon transcript expression, but this alone is insufficient to trigger secretion of immunoglobulin E (IgE). The second signal is provided by a physical interaction between B-cells and activated T-cells, basophils and mast cells, and it has been shown that the CD40/CD40 ligand (CD40L) pairing is crucial for mediating IgE synthesis. In hyper-immunoglobulin M1 (HIGM1) syndrome, which is characterized by greatly decreased levels of immunoglobulin G, A and E (IgG, IgA and IgE), there are mutations in the CD40L resulting in a completely non-functional extracellular domain. The CD40L is, therefore, playing a central role in immunoglobulin isotype switching. Amongst the numerous pairs of surface adhesion molecules, the CD23-CD21 pair seems to play a key role in the generation of IgE. The CD23 molecule is positively and negatively regulated by factors which increase or decrease IgE production, respectively. Antibodies to CD23 have been shown to inhibit IL-4-induced human IgE production in vitro and to inhibit antigen-specific IgE responses in a rat model, in an isotype selective manner. CD23 interacts with CD21 on B-cells, preferentially driving IgE production. CD23 recognizes two main epitopes on the CD21 molecule. One region consists of short consensus repeat (SCR) sequences 1-2 and the other of SCR 5-8. In the latter region, Asn 370 and 295 are critical in the interaction with the lectin CD23. Therefore, a restricted number of cytokines and surface molecules seems to selectively regulate human immunoglobulin E synthesis.

PMID:
8871046
[Indexed for MEDLINE]

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