Abstract
The bursa of Fabricius (BF) is the acknowledged central humoural immune organ unique to birds and plays a vital role in B lymphocyte development. In addition, the unique molecular immune features of bursal-derived biological peptides involved in B cell development are rarely reported. In this paper, a novel bursal heptapeptide (BP7) with the sequence GGCDGAA was isolated from the BF and was shown to enhance the monoclonal antibody production of a hybridoma. A mouse immunization experiment showed that mice immunized with an AIV antigen and BP7 produced strong antibody responses and cell-mediated immune responses. Additionally, BP7 stimulated increased mRNA levels of sIgM in immature mouse WEHI-231 B cells. Gene microarray results confirmed that BP7 regulated 2465 differentially expressed genes in BP7-treated WEHI-231 cells and induced 13 signalling pathways and various immune-related functional processes. Furthermore, we found that BP7 stimulated WEHI-231 cell autophagy and AMPK-ULK1 phosphorylation and regulated Bcl-2 protein expression. Finally, chicken immunization showed that BP7 enhanced the potential antibody and cytokine responses to the AIV antigen. These results suggested that BP7 might be an active biological factor that functions as a potential immunopotentiator, which provided some novel insights into the molecular mechanisms of the effects of bursal peptides on immune functions and B cell differentiation.
Highlights
The most significant contribution that studies on the avian immune system have made to the development of mainstream immunology has been delineating the two major arms of the adaptive immune system, namely, humoural and cellular immunity [1–4]
By aligning the sequence of BP7 in the non-redundant and Expressed Sequence Tag databases of NCBI, we found that BP7 was similar to proteins from Gallus gallus and mice, suggesting that BP7 was conserved in both these species and was probably a proteolytic degradation fragment of an intact protein; there were two proteins of interest in G. gallus (Additional file 3) including interferon-induced helicase C domain-containing protein 1 (IFIH1; NP_001180567.1) and immunoglobulin heavy chain variable region (IGHV; CAO79246.1)
The results showed that compared to control treatment, BP7 treatment enhanced the monoclonal antibody production levels of the hybridoma cells by ELISA (Figure 1C), in which the antibody levels were increased by 45.91%, 52.1% and 27.55% at 0.01, 0.1 and 1 μg/mL BP7 treatment, respectively
Summary
The most significant contribution that studies on the avian immune system have made to the development of mainstream immunology has been delineating the two major arms of the adaptive immune system, namely, humoural and cellular immunity [1–4]. B cell development occurs in three distinct stages, namely, pre-bursal, bursal and post-bursal stages, and each of these stages plays a fundamentally different role in B cell development [5]. Liu et al [6] reported the transcriptional changes in mRNA expression in different developmental stages in the BF. A complete understanding of the anatomy and function of the BF is lacking, and the mechanism underlying the involvement of the BF in B cell development still needs to be profoundly elucidated. B cell differentiation and antibody diversification are accompanied by the regulation of biologically active molecules and activation of immune induction [4].
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