Abstract
The bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which is vital to B cell differentiation and antibody production. However, the function and mechanism of the biological active peptide isolated from bursa on B cell development and autophagy were less reported. In this study, we isolated a new oligopeptide with nine amino acids Leu-Met-Thr-Phe-Arg-Asn-Glu-Gly-Thr from avian bursa following RP-HPLC, MODIL-TOP-MS, and MS/MS, which was named after BP9. The results of immunization experiments showed that mice injected with 0.01 and 0.05 mg/mL BP9 plus JEV vaccine generated the significant increased antibody levels, compared to those injected with JEV vaccine only. The microarray analysis on the molecular basis of BP9-treated immature B cell showed that vast genes were involved in various immune-related biological processes in BP9-treated WEHI-231 cells, among which the regulation of cytokine production and T cell activation were both major immune-related processes in WEHI-231 cells with BP9 treatment following network analysis. Also, the differentially regulated genes were found to be involved in four significantly enriched pathways in BP9-treated WEHI-231 cells. Finally, we proved that BP9 induced the autophagy formation, regulated the gene and protein expressions related to autophagy in immature B cell, and stimulated AMPK-ULK1 phosphorylation expression. These results suggested that BP9 might be a strong bursal-derived active peptide on antibody response, B cell differentiation, and autophagy in immature B cells, which provided the linking among humoral immunity, B cell differentiation, and autophagy and offered the important reference for the effective immunotherapeutic strategies and immune improvement.
Highlights
The bursa of Fabricius (BF) of chicken is a foundational model for immunology research, which provides some valuable insights into the central humoral immune function for human and mammal
In this paper, following RP-HPLC and MALDI-TOF-MS, we found the strong elution peak at 11.19 min (Figure 1(a)), a new polypeptide isolated from avian BF, whose molecular weight was 1068.22 mz
We found that among the top 50 significant value of Gene Ontology (GO) terms, 38 terms were belonged to biological process, 9 terms were belonged to cellular component, and the other 3 terms were belonged to molecular function (Figure 3(c))
Summary
The bursa of Fabricius (BF) of chicken is a foundational model for immunology research, which provides some valuable insights into the central humoral immune function for human and mammal. B cell differentiation and immunoglobulin diversification were accompanying with regulation of biological active molecular and activation of Journal of Immunology Research immune induction [8]. Bursal pentapeptide-II (BPP-II) and BP5 regulated various pathways and immune-related biological processes in hybridoma cells secreting monoclonal antibody especial to JEV [15, 16]. B cell differentiation and development are the complex biological processes, including various gene expressions, gene regulation, and signal activation. Investigation of the immune induction of bursal-derived peptide had primarily been conducted following mouse immunization and immature B cell model, whereas little was known about the molecular basis of bursal peptides on immature B cell development and autophagy
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