Divergent antibody isotype responses induced in mice by systemic exposure to proteins: a comparison of ovalbumin with bovine serum albumin

Whereas many Foreign proteins are immunogenic, only a proportion is associa ted commonly with allergy, having the potential to induce the quality of im mune response necessary for IgE antibody production and the development of immediate type hypersensitivity reactions in the gastrointestinal and/or re spiratory tracts. In the contest of toxicological evaluations there is a ne ed to identify those properties that confer on proteins the ability to prov oke allergic reactions. The characteristics of antibody responses induced i n BALB/c strain mice following administration of ovalbumin (OVA), a signifi cant human allergen, have been compared with those provoked by bovine serum albumin (BSA), a protein considered to have more limited allergenic potent ial. Intranasal or intraperitoneal (ip) administration of BSA or OVA elicit ed vigorous IgG and IgG1 antibody responses. Differential IgE antibody prod uction was observed, however, with OVA stimulating relatively high IgE anti body titres at all doses tested whereas no or low titre IgE antibody was de tected following exposure to BSA. Furthermore, a differential capacity for IgG2a antibody responses was observed, with only BSA provoking high titres of this Ige subclass. The relative quality of induced responses was equival ent following administration of these proteins, ia mucosal (in) tissue or v ia a non-mucosal (ip) route of exposure. IgG2a antibody production is promo ted by the tS pe I cytokine interferon gamma (IFN-gamma), whereas IFN-gamma and the type 2 cell product interleukin 4 exert reciprocal antagonistic ef fects on IgE antibody responses. Although cytokine expression patterns were not analysed in this series of experiments, the differential IgE and Ige s ubclass antibody responses induced by BSA and OVA are consistent with the p referential activation of T helper (Th) 1- and Th2-type cells, respectively . These data indicate that proteins ran provoke in mice characteristic anti body (IgE and IgG) isotype profiles suggestive of discrete T lymphocyte res ponses and that such differences may be associated with variable allergenic activity. (C) 2000 Elsevier Science Ltd. All rights reserved.