Abstract
The bursa of Fabricius, the key humoral immune organ unique to birds, is critical for B cell differentiation and antibody production. BP8 (AGHTKKAP) is a novel immunomodulatory peptide that regulates B-cell development. Gene microarray was used to investigate the mechanism of BP8 on B cell development. BP8 regulated expressions of 1,570 genes that were involved in retinol metabolism, the Wnt signaling pathway, MAPK pathway, Jak–Stat pathway, Notch signaling pathway, cytokine–cytokine receptor interaction, and Ca2+ signals. Finally, BP8 triggered ADH7 and RDH10 expression, interacted with retinol binding protein, and regulated retinol uptake in vitro and vivo. These data reveal a bursal-derived multifunctional factor, BP8, as a novel biomaterial which is essential for the development of the immune system and represents an important linker between the B cell development and retinol metabolism. This study elucidates the mechanisms involved in humoral immune system and has implications in treating human diseases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776
Brand A, Gilmour DG, Goldstein G (1976) Lymphocyte-differentiating hormone of bursa of Fabricius. Science 193:319–321
Chute JP, Muramoto GG, Whitesides J, Colvin M, Safi R, Chao NJ, McDonnell DP (2006) Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci USA 103:11707–11712
Cooper MD, Peterson RD, South MA, Good RA (1966) The functions of the thymus system and the bursa system in the chicken. J Exp Med 123:75–102
Davison F, Kaspers B, Schat KA, Kaiser P (2011) Avian immunology. Access Online via Elsevier, London, pp 1–20
Farjo KM, Moiseyev G, Nikolaeva O, Sandell LL, Trainor PA, Ma J-X (2011) RDH10 is the primary enzyme responsible for the first step of embryonic Vitamin A metabolism and retinoic acid synthesis. Dev Biol 357:347–355
Feske S (2007) Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 7:690–702
Fine J, Macosko H, Grace M, Narula S (1994) Influence of IL-10 on murine CFU-pre-B formation. Exp Hematol 22:1188–1196
Fritzenwanger M, Meusel K, Foerster M, Kuethe F, Krack A, Figulla HR (2006) Cardiotrophin-1 induces interleukin-6 synthesis in human umbilical vein endothelial cells. Cytokine 36:101–106
Fritzenwanger M, Meusel K, Foerster M, Kuethe F, Krack A, Figulla H-R (2007) Cardiotrophin-1 induces interleukin-6 synthesis in human monocytes. Cytokine 38:137–144
Glick B, Chang TS, Jaap RG (1956) The bursa of Fabricius and antibody production. Poult Sci 35:224–225
Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H et al (2007) A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315:820–825
Liu XD, Zhou B, Feng XL, Cao RB, Chen PY (2014) BP8, a novel peptide from avian immune system, modulates B cell developments. Amino Acids. doi:10.1007/s00726-014-1824-x
Lydyard PM, Grossi CE, Cooper M (1976) Ontogeny of B cells in the chicken. I. Sequential development of clonal diversity in the bursa. J Exp Med 144:79–97
Mora JR, Iwata M, von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8:685–698
Nie L, Perry SS, Zhao Y, Huang J, Kincade PW, Farrar MA, Sun X-H (2008) Regulation of lymphocyte development by cell-type-specific interpretation of Notch signals. Mol Cell Biol 28:2078–2090
Ranheim EA, Kwan HC, Reya T, Wang Y-K, Weissman IL, Francke U (2005) Frizzled 9 knock-out mice have abnormal B-cell development. Blood 105:2487–2494
Rincón M (2001) MAP-kinase signaling pathways in T cells. Curr opinion Imm 13:339–345
van de Pavert SA, Mebius RE (2010) New insights into the development of lymphoid tissues. Nat Rev Immunol 10:664–674
Zgombic-Knight M, Foglio MH, Duester G (1995) Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro. J Biol Chem 270:4305–4311
Acknowledgments
This work was supported by the Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the National Special Research Programs for Non-profit Trades, Ministry of Agriculture (No. 201203082) and international S&T Cooperation Program of China (ISTCP) (No. 2014DFR30980). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Supporting information
Supplementary Table 1—Q-PCR primers of involved genes.
Supplementary Table 2—Pathway assay of genes up-regulated and down-regulated with BP8 treatment in B cells
Conflict of interest
The authors declared no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Liu, XD., Zhang, FB., Shan, H. et al. The potential mechanism of bursal-derived BP8 on B cell developments. Biotechnol Lett 37, 1013–1020 (2015). https://doi.org/10.1007/s10529-015-1772-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-015-1772-x