Bovine milk IgG, the major xenogeneic immunoglobulin found in the human diet (often 500 mg/day), is sometimes significantly absorbed in humans and selectively found in human breast milk. Bovine milk IgG has an unusual specificity pattern for some human FcGamma receptors and has immunomodulatory properties in vitro. Our major aim is to test a hypothesis (consistent with epidemiologic data) that dietary bovine IgG, possibly in conjunction with human antibodies, may significantly influence human responses in vivo and may play a role in the pathogenesis of some human immunologic diseases. We plan: (1) To study mechanisms by which bovine milk IgG inhibits antibody secretion from pokeweed mitogen stimulated human peripheral blood mononuclear cells in vitro, and B cell maturation pathway sites of inhibition. Human mononuclear cells will be cultured with bovine IgG preparations to characterize the subclass region, and aggregate size of IgG and the cell types involved in the observed inhibition. To evaluate effects of bovine IgG on spontaneous antibody secretion, mitogenesis, MLR, and cytotoxicity. (2) To examine bovine milk IgG inhibition of mouse plaque-forming cell (PFC) responses in vitro with studies not possible in the human system. To evaluate effects of in vivo and in vitro exposure of mouse cells on LPS-induced and antigen-specific PFC responses, to compare inhibitory effects of bovine, human and mouse IgG subclasses, to examine mechanisms of inhibition and possible suppressor cells and/or factors. (3) To measure bovine IgG levels and molecular size of bovine IgG-containing fractions in human breast milk in mothers of normal infants and mothers of infants with colic. To study proteolysis, absorption, cellular association, transplacental and transmammary passage, and serum half-life of bovine IgG in humans and animal models. (4) To determine whether bovine IgG exposures, serum levels of bovine IgG, or antibodies to bovine IgG are related to the occurrence and severity of infantile colic, of eosinophilic gastroenteritis, and, in preliminary studies, of ulcerative colitis.
These aims will further our long term objectives: (1) Studying regulation of immune responses by IgG via FcGammaR, esp. the effects of bovine IgG from dietary sources on human immune responses in vitro and in vivo. (2) Examine potential roles of bovine IgG and of human immune responses to it in the pathogenesis of infantile colic, eosinophilic gastroenteritis, and ulcerative colitis.
|Clyne, P S; Kulczycki Jr, A (1991) Human breast milk contains bovine IgG. Relationship to infant colic? Pediatrics 87:439-44|
|Kulczycki Jr, A; Webber, J; Soares, H A et al. (1990) Genomic organization of mouse Fc gamma receptor genes. Proc Natl Acad Sci U S A 87:2856-60|