Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

The Inducing Role and Molecular Basis of Bursal Hexapeptide (BHP) on Avian Immature B Cell

Author(s): Xiu Li Feng*, Yang Zheng, Shan Shan Hao, Guang Fang Zhou and Pu Yan Chen

Volume 26, Issue 5, 2019

Page: [348 - 356] Pages: 9

DOI: 10.2174/0929866526666190228141650

Price: $65

Abstract

Background: The Bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which provides an ideal research model on the immature B cell development.

Objective: In this article, our motivation is to study the role on sIgM and establish the molecular basis and functional processes of Bursal Hexapeptide (BHP) in avian immature B cells DT40 cell lines.

Methods: In this article, we detected the expressions of sIgM mRNA with qPCR in DT40 cells with BHP treatment, and investigated the gene expression profiles of BHP-treated DT40 cells, employing microarray analyses. Also, to validate the differentially expressed genes, we performed KEGG pathway and Gene Ontology analysis in the BHP-treated DT40 cells. Finally, we comparatively analyzed the similar regulated genes and their involved immune functional processes between DT40 cell and mouse immature B cell line WEHI231 cell with BHP treatment.

Results: Following the proposed framework, we proved that the BHP enhanced the mRNA expression levels of IgM in DT40 cells, and induced 460 upregulated genes and 460 downregulated genes in BHP-treated DT40 cells. The pathway analysis showed that the differentially regulated genes in DT40 cell line with BHP treatment were involved in 12 enrichment pathways, in which Toll-like receptor signaling pathway was the vital pathways, and cytokine-cytokine receptor interaction and Jak-STAT signaling pathway were another two important pathways in BHP-treated DT40 cells. Moreover, BHP induced the immune related biological processes in BHP-treated DT40 cells, including T cell related, cytokine related, lymphocyte related, and innate immune response GO terms. Finally, the comparatively analysis showed that there were two downregulated genes GATA3 and IFNG to be found co-existed among the differentially expressed genes in BHP-treated DT40 cell and WEHI231 cells, which shared some same immune related functional processes in both cell lines.

Conclusion: After the applying the framework, we proved the inducing roles and the gene expression profiles of BHP on avian immature B cells, and verified some molecular basis from the KEGG and GO analysis. These results provided the insight for mechanism on immature B cell differentiation, and offer the essential direction for the vaccine improvement.

Keywords: Bursal Hexapeptide (BHP), IgM, immature B cell, pathways, immune functional processes, toll-like receptor signaling pathway.

Graphical Abstract

[1]
Cooper, M.D.; Peterson, R.D.; Good, R.A. Delineation of the thymic and bursal lymphoid systems in the chicken. Nature, 1965, 205, 143-147.
[2]
Butler, J.E.; Sinkora, M. The enigma of the lower Gut-Associated Lymphoid Tissue (GALT). J. Leukoc. Biol., 2013, 94, 259-270.
[3]
Ratcliffe, M.J.H. B cell development in gut associated lymphoid tissues. Vet. Immunol. Immunopathol., 2002, 87, 337-340.
[4]
Korte, J.; Fröhlich, T.; Kohn, M.; Kaspers, B.; Arnold, G.J.; Härtle, S. 2D DIGE analysis of the Bursa of Fabricius reveals characteristic proteome profiles for different stages of chicken B-cell development. Proteomics, 2013, 13, 119-133.
[5]
Ratcliffe, M.J.H.; Hartle, S.B. Cells, the Bursa of fabricius and the generation of antibody repertoires. In: Avian Immunology; 2nd Edition; Schat, K.A.; Kaspers, B.; Kaiser, P.; Eds; Academic Press, Elsevier: Cambridge, MA, 2014; p. 65.
[6]
Ekino, S.; Sonoda, K.; Inui, S. Origin of IgM(+) IgG(+) lymphocytes in the Bursa of Fabricius. Cell Tissue Res., 2015, 362, 153-162.
[7]
Ekino, S.; Sonoda, K. New insight into the origin of IgG-bearing cells in the Bursa of Fabricius. Int. Rev. Cell Mol. Biol., 2014, 312, 101-137.
[8]
Brand, A.; Cilmour, D.G.; Coldstein, G. Lymphocyte - differentiating hormone of Bursa of Fabricius. Science, 1976, 193, 319-321.
[9]
Audhya, T.; Kroon, D.; Heavner, G.; Viamontes, G.; Goldstein, G. Tripeptide structure of bursin, a selective B-cell-differentiating hormone of the Bursa of Fabricius. Science, 1986, 231, 997-999.
[10]
Baba, T.; Kita, M. Effect of extracts of the Bursa of Fabricius on IgG antibody production in hormonally bursectomized chicken. Immunology, 1977, 32, 271-274.
[11]
Liu, X.D.; Zhou, B.; Feng, X.L.; Cao, R.B.; Chen, P.Y. BP8, a novel peptide from avian immune system, modulates B cell developments. Amino Acids, 2014, 46, 2705-2713.
[12]
Liu, X.D.; Zhang, F.B.; Shan, H.; Chen, P.Y. The potential mechanism of bursal-derived BP8 on B cell developments. Biotechnol. Lett., 2015, 37, 1013-1020.
[13]
Feng, X.L.; Liu, Q.T.; Cao, R.B.; Zhou, B.; Ma, Z.Y.; Deng, W.L.; Wei, J.C.; Qiu, Y.F.; Wang, F.Q.; Gu, J.Y.; Wang, F.J.; Zheng, Q.S.; Ishag, H.; Chen, P. Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II). J. Biol. Chem., 2012, 287, 3798-3807.
[14]
Feng, X.; Cao, R.; Zhou, B.; Liu, Q.; Liu, K.; Liu, X.; Zhang, Y.; Gu, J.; Miao, D.; Chen, P. The potential mechanism of Bursal-derived BPP-II on the antibody production and avian pre-B cell. Vaccine, 2013, 31, 1535-1539.
[15]
Feng, X.L.; Zhou, B.; Cao, R.B.; Liu, Q.T.; Liu, K.; Liu, X.D.; Zhang, Y.P.; Huang, L.; Ji, X.B.; Luo, J.; Zhang, G.; Chen, P.Y. Immunomodulatory roles and functional analysis of pre-B lymphocyte DT40 cells with the bursal-derived BSP-II treatment. Peptides, 2012, 36, 292-298.
[16]
Liu, X.D.; Zhou, B.; Cao, R.B.; Feng, X.L.; Ma, Z.Y.; Chen, P.Y. BP5 regulated B cell development promoting anti-oxidant defence. Amino Acids, 2014, 46, 209-222.
[17]
Ratcliffe, M.J.H. Antibodies, immunoglobulin genes and the Bursa of Fabricius in chicken B cell development. Dev. Comp. Immunol., 2006, 30, 101-118.
[18]
Molnár, J.; Póti, Á.; Pipek, O.; Krzystanek, M.; Kanu, N.; Swanton, C.; Tusnády, G.E.; Szallasi, Z.; Csabai, I.; Szüts, D. The genome of the chicken DT40 bursal lymphoma cell line. G3 (Bethesda), 2014, 4, 2231-2240.
[19]
Caldwell, R.B.; Kierzek, A.M.; Arakawa, H.; Bezzubov, Y.; Zaim, J.; Fiedler, P.; Kutter, S.; Blagodatski, A.; Kostovska, D.; Koter, M.; Plachy, J.; Carninci, P.; Hayashizaki, Y.; Buerstedde, J.M. Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis. Genome Biol., 2005, 6, R6.
[20]
Kim, S.; Humphries, E.H.; Tjoelker, L.; Carlson, L.; Thompson, C.B. Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line. Mol. Cell. Biol., 1990, 10, 3224-3231.
[21]
Zong, M.M.; Zhou, G.F.; Zheng, Y.; Yu, Y.N.; Zhou, C.J.; Feng, X.L.; Cao, R.B.; Chen, P.Y.; Yang, M. The functions of bursal hexapeptide (bhp) on immune response and the molecular mechanism on immature B cell. Protein Pept. Lett., 2018, 24, 1130-1140.
[22]
Marshall, D.R.; Olivas, E.; Andreansky, S.; La Gruta, N.L.; Neale, G.A.; Gutierrez, A.; Wichlan, D.G.; Wingo, S.; Cheng, C.; Doherty, P.C.; Turner, S.J. Effector CD8+T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression. Proc. Natl. Acad. Sci. USA, 2005, 102, 6074-6079.
[23]
Mastrangeli, R.; Palinsky, W.; Bierau, H. How unique is interferon-β within the type I interferon family? Cytokine, 2018, 111, 206-208.
[24]
Sun, L.; He, C.; Nair, L.; Yeung, J.; Egwuagu, C.E. Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease. Cytokine, 2015, 75, 249-255.
[25]
Liu, D.; Xu, H.; Shih, C.; Wan, Z.; Ma, X.; Ma, W.; Luo, D.; Qi, H. T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature, 2015, 517, 214-218.
[26]
Grewal, I.S.; Flavell, R.A. The role of CD40 ligand in costimulation and T-cell activation. Immunol. Rev., 1996, 153, 85-106.
[27]
Jeurissen, A.; Billiau, A.D.; Moens, L.; Shengqiao, L.; Landuyt, W.; Wuyts, G.; Boon, L.; Waer, M.; Ceuppens, J.L.; Bossuyt, X. CD4+ T lymphocytes expressing CD40 ligand help the IgM antibody response to soluble pneumococcal polysaccharides via an intermediate cell type. J. Immunol., 2006, 176, 529-536.
[28]
Silverstein, A.M. The lymphocyte in immunology: From James B. Murphy to James L. Gowans. Nat. Immunol., 2001, 2, 569-571.
[29]
Soleto, I.; Morel, E.; Martín, D.; Granja, A.G.; Tafalla, C. Regulation of IgM+ B cell activities by rainbow trout April reveals specific effects of this cytokine in lower vertebrates. Front. Immunol., 2018, 9, 1880.
[30]
Sullivan, N.L.; Eickhoff, C.S.; Zhang, X.; Giddings, O.K.; Lane, T.E.; Hoft, D.F. Importance of the CCR5-CCL5 axis for mucosal Trypanosoma cruzi protection and B cell activation. J. Immunol., 2011, 187, 1358-1368.
[31]
Tian, M.; Hua, Z.; Hong, S.; Zhang, Z.; Liu, C.; Lin, L.; Chen, J.; Zhang, W.; Zhou, X.; Zhang, F.; DeFranco, A.L.; Hou, B. B cell-intrinsic MyD88 signaling promotes initial cell proliferation and differentiation to enhance the germinal center response to a virus-like particle. J. Immunol., 2018, 200, 937-948.
[32]
Sweet, R.A.; Nickerson, K.M.; Cullen, J.L.; Wang, Y.; Shlomchik, M.J. B cell-extrinsic Myd88 and Fcer1g negatively regulate autoreactive and normal B cell immune responses. J. Immunol., 2017, 199, 885-893.
[33]
Tanabe, K.; Inui, S. Dominant negative form of alpha4 inhibits the BCR cross linking-induced phosphorylation of Bcl-xL and apoptosis in an immature B cell line WEHI-231. Biomed. Res., 2015, 36, 97-102.
[34]
Tindemans, I.; Serafini, N.; Di Santo, J.P.; Hendriks, R.W. GATA-3 function in innate and adaptive immunity. Immunity, 2014, 41, 191-206.
[35]
Naito, T.; Tanaka, H.; Naoe, Y.; Taniuchi, I. Transcriptional control of T-cell development. Int. Immunol., 2011, 23, 661-668.
[36]
Patrone, L.; Damore, M.A.; Lee, M.B.; Malone, C.S.; Wall, R. Genes expressed during the IFN gamma-induced maturation of pre-B cells. Mol. Immunol., 2002, 38, 597-606.
[37]
O’Neil, D.; Swanton, C.; Jones, A.; Medd, P.G.; Rayment, N.; Chain, B. IFN-gamma down-regulates MHC expression and antigen processing in a human B cell line. J. Immunol., 1999, 162, 791-798.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy