Role of IL-4 in persistent IgE formation.
Antigen-specific immunoglobulin E (IgE) responses against T-cell-dependent antigens, like allergens, can only be generated by cognate interaction between B-cells and T-helper (Th2) cells. This interaction is a prerequisite, donating the two signals that are essential for IgE production: CD40 ligation with its ligand gp39 and exposure to interleukin (IL)-4. Cytokine-mediated immunotherapy geared at intervention in allergic diseases, therefore aims at inhibiting the production or action of IL-4. In our view, based on two findings, this approach is simplistic. The first is that anti-IL-4 based approach (by complex formation between IL-4 and soluble IL-4 receptors or serum binding proteins) may actually increase the persistence of IL-4 and its effects instead of inhibiting them. Secondly, we have good evidence in mouse model systems that a period of exposure to IL-4 will result in an increased population of gamma 1,epsilon-double positive B-cells allowing an increased serum IgE level to persist for extensive periods of time. These B-cells turn out to be partially independent of IL-4 for their IgE formation. Moreover, these B-cells are partially independent of a cognate interaction with T-cells for their subsequent IgE synthesis. Therefore, we hypothesize that an approach geared solely at inhibiting IL-4 is not sufficient for decreasing persistent IgE levels in allergic patients.
Savelkoul
H F
HF
Dept of Immunology, Erasmus University, Rotterdam, The Netherlands.
van Ommen
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002450:Cell Communication; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D006967:Hypersensitivity / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007167:Immunotherapy; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D019013:CD40 Antigens; D016207:Cytokines; D015847:Interleukin-4; D007073:Immunoglobulin E