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

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.

Bonnefoy JY ，Gauchat JF ，Life P ，Graber P ，Mazzei G ，Aubry JP ... -  《-》

Regulation of IgE synthesis by CD23/CD21 interaction.

Bonnefoy JY ，Gauchat JF ，Life P ，Graber P ，Aubry JP ，Lecoanet-Henchoz S ... -  《INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY》

Stimulation of human IgE production by a subset of anti-CD21 monoclonal antibodies: requirement of a co-signal to modulate epsilon transcripts.

Henchoz S ，Gauchat JF ，Aubry JP ，Graber P ，Pochon S ，Bonnefoy JY ... -  《-》

Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signaling pathways.

Gascan H ，Gauchat JF ，Aversa G ，Van Vlasselaer P ，de Vries JE ... -  《JOURNAL OF IMMUNOLOGY》

Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.

Saiki O ，Tanaka T ，Wada Y ，Uda H ，Inoue A ，Katada Y ，Izeki M ，Iwata M ，Nunoi H ，Matsuda I ... -  《JOURNAL OF CLINICAL INVESTIGATION》