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

Publisher Website
Google Scholar
Abstract
Immunoglobulin E (IgE; see ref. 1) has a central role in allergic reactions although it rarely exceeds 5 µg 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 mediators including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera2; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells3–5 has allowed us to construct a mouse cell line that secretes a chimaeric IgE, λ1 antibody whose heavy chain is composed of a human Cε 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.