The IgG is

then released into the fetal circulation.4 The FcRn is also expressed on the intestinal epithelium and mediates the transepithelial transfer of the IgG1 present in the maternal milk to the circulation of the progeny.5 Transplacentally acquired maternal IgG is important for protection of infants in the early Akt inhibitor months of life from bacterial or viral infections. The transfer of maternal antigen-specific IgG has also been shown to influence antigen-specific immune responses later in the life of the progeny. Hence, the transfer of maternal IgG bearing a κ light chain to κ-light-chain-deficient fetuses has been shown to alter in an antigen-dependent manner the repertoires of T lymphocytes.6 Further, the transfer of maternal anti-idiotypic IgG directed against anti-phosphorylcholine (PC) antibodies has been shown to skew the repertoires of PC-specific B lymphocytes after immunization of the offspring with PC later in life.7 In addition, the passive transfer

of maternal IgG during pregnancy has been occasionally shown to impair vaccination in early infancy, probably as the result of the neutralization of the immunogen by the transferred IgG.8 Here, using a mouse model of haemophilia MK 2206 A, we investigated whether maternal anti-FVIII IgG transferred during the ontogeny of the immune system of the progeny may modulate the capacity to develop an anti-FVIII immune response later in adulthood. Mice were 7- to 10-week-old inbred 129 × C57BL/6 (H-2Db background) exon 16 FVIII-deficient males and females (a gift from Prof. Kazazian, University of Pennsylvania School of Medicine, Philadelphia). Animals were handled in agreement with local ethical authorities (Comité regional d’éthique p3/2008/024). Mice were administered human recombinant FVIII (1 IU; Helixate®, CSL-Behring, Marburg, Germany) diluted in phosphate-buffered saline (PBS) or PBS only by retro-orbital intravenous injection once a week for up to 6 weeks. Alternatively, mice were immunized by a subcutaneous injection of ovalbumin

(OVA, 50 μg, grade VII; Sigma, St Louis, MO) in complete Freund’s adjuvant CYTH4 followed by two injections of OVA (50 μg) in incomplete Freund’s adjuvant with a weekly interval. Blood was collected by retro-orbital puncture 5 days after each administration of FVIII or the last immunization with OVA. Serum was kept at − 20° until use. Groups of five to seven mice were used in each set of experiments. Plates for enzyme-linked immunosorbent assay (ELISA; Nunc, Roskilde, Denmark) were coated with rFVIII (2 μg/ml; Recombinate®, Baxter, Maurepas, France) or with OVA (2 μg/ml, grade V; Sigma) overnight at 4°, and blocked with PBS, 1% bovine serum albumin or with PBS, 1% milk, respectively. Serum dilutions were then incubated for 1 hr at 37°. Bound IgG was revealed using a horseradish peroxidase-coupled monoclonal anti-mouse IgG (Southern Biotech, Anaheim, CA, USA) and substrate.