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

Protein Pept Lett. 2019;26(5):348-356. doi: 10.2174/0929866526666190228141650.

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; immune functional processes; pathways; toll-like receptor signaling pathway..

MeSH terms

  • Animals
  • Bursa of Fabricius
  • Cell Line
  • Chickens
  • Immunity, Innate
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism
  • Mice
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacology
  • Precursor Cells, B-Lymphoid / drug effects
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Species Specificity
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Immunoglobulin M
  • Oligopeptides
  • RNA, Messenger