Effect of Maternal Dietary Cow’s Milk on the Immune Response to β-Lactoglobulin in the Offspring: A Four-Generation Study in Mice

Abstract

Background: Evaluation of immune responses to food proteins in animal models requires that the animals are not already sensitized or orally tolerized against the proteins in question. Since maternal transfer of specific immune responses has been observed, breeding of animals on an antigen-free diet for several generations may be necessary to obtain immunologically naïve animals. Methods: To determine the most appropriate breeding conditions of mice to be used in immunological studies on food proteins, we examined immune responses towards β-lactoglobulin (BLG) in mice bred on a milk-containing diet (F0) and then for three generations (F1–F3) on a commercially available milk-free diet. The specific antibody and cell-proliferative response to BLG was compared in non-immunized and immunized BALB/c mice, and in mice orally tolerized to BLG prior to immunization. Results: The immune response to BLG in the F1 generation deviated from the response observed in the F0 and F2/F3 generations. Importantly, trace amounts of BLG detected in the commercial milk-free diet did not induce oral tolerance. Conclusions: The study showed that breeding mice on an antigen-free diet for at least two generations is required to attain animals appropriate for immunological studies of food proteins. Although the small quantity of BLG in the milk-free diet did not induce detectable oral tolerance in the present study, it is strongly recommended that the potential effect of contaminating dietary antigen is considered in future studies on food proteins.

Sensitization with 7S Globulins from Peanut, Hazelnut, Soy or Pea Induces IgE with Different Biological Activities Which Are Modified by Soy Tolerance

“…If rats are fed a diet in which the major components are milk or soy, the rats will have specific IgG to these dietary components [37,38]. Such animals are unsuited for oral or low-dose i.p.…”

Transgenerational developmental programming

“…Other studies report effects on blood pressure and vascular dysfunction (Anderson et al, 2006;Armitage et al, 2007;Costantine et al, 2008;Torrens et al, 2008;Harrison and Langley-Evans, 2009). Apart from components of the metabolic syndrome, the studies reviewed here include those with outcomes relating to immune function (Beach et al, 1982;Brix et al, 2005;Csaba et al, 2005;Pallinger et al, 2006), reproduction (Chernoff et al, 2009;Fullston et al, 2012) and neurological aspects of development (Lam et al, 2000;Slamberova et al, 2005;Stone and Bales, 2010). Despite careful analyses of these parameters in different studies, there remains significant variation in the phenotypic characteristics transmitted to the F2 generation; these may be diet or timing dependent, or may be influenced by the rodent (rat v mouse) or strain used.…”

Immunogenicity of κ-Casein and Glycomacropeptide

“…Female BALB/c mice, 5 to 6 wk old, were kept in standard animal housing and fed a diet containing very low levels of milk components (Harlan Teklad, Teklad, UK; Brix et al, 2005) and water ad libitum. Two experiments were carried out.…”