A novel immunoregulatory protein in human colostrum, syntenin-1, for promoting the development of IgA-producing cells from cord blood B cells.

Human colostrum contains many bioactive factors that must promote the development of intestinal mucosal immunity in infants. Especially, the presence of certain cytokines such as transforming growth factor (TGF)-beta or IL-10 has been of great interest for IgA production as a function of mucosal immune response. In the present study, we attempted to investigate whether unidentified factors inducing generation of IgA-producing cells from naive B cells might exist in colostrum. For this purpose, colostrum samples were directly added to a culture consisting of naive B cells and dendritic cells from cord blood and CD40 ligand-transfected L cells, comparing with recombinant IL-10 (rIL-10) and/or rTGF-beta. It was noted that most colostrum samples alone were able to induce IgA-secreting cells at higher levels than rIL-10 and/or rTGF-beta. IgA-inducing activity of colostrum was abolished by neither anti-neutralizing mAbs against IL-10 nor TGF-beta, though partially by anti-IL-6 mAb. We prepared partially purified fractions from both pooled colostrums with and without IgA-inducing activity and comparatively performed quantitative proteomic analysis by two-dimensional difference gel electrophoresis followed by liquid chromatography-mass spectrometry. As a result, syntenin-1 was identified as a candidate for IgA-inducing protein in colostrum. Western blot analysis indicated that levels of syntenin-1 in colostrum samples were correlated with their IgA-inducing activities. Moreover, we demonstrated that recombinant syntenin-1 could induce preferentially IgA production from naive B cells. These results suggest that syntenin-1 serves as one of IgA-inducing factors for B cells.

Role of transforming growth factor-beta in breast milk for initiation of IgA production in newborn infants.

BACKGROUND: Transforming growth factor (TGF)-beta has a crucial effect on IgA production, which is the major humoral effector of mucosal immunity. Breast milk contains the abundant amount of TGF-beta in the early period of lactation. AIM-STUDY DESIGN: To verify the notion that TGF-beta in breast milk might contribute to the development of IgA production in newborns, we investigated the association of TGF-beta in maternal colostrum with an increase of serum IgA in newborns during the first month of life. SUBJECTS AND METHODS: The concentrations of TGF-beta1 and TGF-beta2, including IL-6 and IL-10, in colostrum samples from 55 healthy mothers were determined by ELISA. The levels of IgA and IgM in serum samples collected from corresponding newborn babies at birth and at 1 month of age were measured by ELISA. RESULTS: TGF-beta1 and TGF-beta2 were detected in substantial quantities in all colostrum samples, but IL-6 and IL-10 were present only in a proportion of samples. An increase of serum IgA in newborn during the first month of life was significantly higher than that of serum IgM (p<0.001). Notably, an increase of serum IgA in newborns during 1 month of life was well correlated with levels of both TGF-beta1 (r=0.38, p=0.005) and TGF-beta2 (r=0.45, p=0.0005) in colostrum, while that of IgM was marginally correlated with colostral TGF-beta2 (r=0.28, p=0.04). The association of increase of serum IgA in newborns with IL-6 and IL-10 in colostrum was not evident. CONCLUSION: Our findings suggest that TGF-beta in colostrum might serve as the starter of IgA production in newborn infants.