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.
Sira
Mostafa M
MM
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan.
Yoshida
Taketoshi
T
Takeuchi
Makoto
M
Kashiwayama
Yoshinori
Y
Futatani
Takeshi
T
Kanegane
Hirokazu
H
Sasahara
Akiko
A
Ito
Yasunori
Y
Mizuguchi
Mineyuki
M
Imanaka
Tsuneo
T
Miyawaki
Toshio
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003126:Colostrum / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D007739:L Cells; D051379:Mice; D011247:Pregnancy; D053676:Syntenins / Q000276:immunology*
D007070:Immunoglobulin A; D053676:Syntenins