A hapten-specific chimaeric IgE antibody with human physiological effector function.

Immunoglobulin E (IgE) has a central role in allergic reactions although it rarely exceeds 5 micrograms ml-1 even in the serum of severely allergic individuals. Both mast cells and basophils possess receptors which bind the Fc portion of IgE with high affinity; crosslinking of membrane-bound IgE by allergen results in degranulation of the cell and release of a variety of pharmacologically active mediator including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells has allowed us to construct a mouse cell line that secretes a chimaeric IgE, lambda 1 antibody whose heavy chain is composed of a human C epsilon constant region fused to a mouse variable (VH) region. This chimaeric IgE is specific for the hapten 4-hydroxy-3-nitro-phenacetyl (NP) and can, when crosslinked by antigen, trigger the degranulation of human basophils. When not crosslinked, however, the chimaeric IgE can prevent the passive sensitization of these cells by sera from allergic subjects.

Basophils in allergen-induced patch test sites in atopic dermatitis.

Atopic dermatitis often occurs in patients who have high IgE levels and positive immediate skin tests to several common allergens. However, there is considerable doubt about the role played by allergens in this disease. Patch testing for 48 h at superficially abraded skin sites revealed that allergens could induce eczematous lesions in atopic dermatitis patients but only in those who also gave a positive immediate skin reaction to the same allergen. Lesions induced by the purified house dust mite antigen, antigen P1 contained mononuclear cells, basophils, eosinophils, and neutrophils. These patients also had raised specific serum IgE against antigen P1, and their leucocytes released histamine upon exposure to the same antigen. Thus an acute eczematous lesion can be induced by the application of inhalant allergens to the skin.

Induction and modification of anti-TNP reaginic and IgG antibody responses by reactive trinitrophenyl derivatives.

The anti-TNP antibody response of mice exposed to picryl chloride is a response where IgE antibody can be preferentially produced. Skin-painting with picryl chloride induces IgM, IgG and IgE antibody. After repeated painting the titre and persistence of the IgE but not IgG antibody is increased. Feeding picryl chloride does not induce antibody but it does produce unresponsiveness for IgG without affecting responsiveness for IgE. Injection of picryl sulphonic acid produces unresponsiveness for both classes. The unresponsiveness (induced by feeding or injection) is found for responses to picryl chloride but responses to TNP-KLH are barely affected. Both the IgE and IgG responses to picryl chloride are initiated in the lymph nodes and then develop in the spleen. IgE and IgG antibody production are both T-cell dependent but not influenced by adult thymectomy.