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. 2019 Sep 18;50(1):64.
doi: 10.1186/s13567-019-0682-7.

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

Xiu Li Feng  1   2 , Yang Zheng  3   4 , Man Man Zong  3   4 , Shan Shan Hao  3   4 , Guang Fang Zhou  3   4 , Rui Bing Cao  3   4 , Pu Yan Chen  3   4 , Qing Tao Liu  5
Affiliations

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

Xiu Li Feng et al. Vet Res. .

Erratum in

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Isolation and identification of BP7. A The isolation and purification of BP7. B MS/MS analysis of the amino acid sequence of BP7. C Antibody production of hybridoma cells enhanced by BP7. Data represent the mean ± standard deviation (s.d.). Significant differences between groups were determined using Student’s t-test, and p < 0.05 is indicated by an asterisk (*).
Figure 2
Figure 2
BP7 induced various immune responses in mice immunized with an AIV antigen. BALB/c mice were immunized with BP7 and an AIV H9N2 antigen following a prime-boost vaccination strategy. A Antibody subtypes, B cytokine production, C T cell populations, and D lymphocyte viability. Data represent the mean ± standard deviation (s.d.). Significant differences between groups were determined using Student’s t-test, where p < 0.05 and p < 0.01 are indicated by asterisks (* and **, respectively).
Figure 3
Figure 3
Roles of BP7 and BP7-induced gene expression profiles in WEHI-231 cells. WEHI-231 cells were treated with BP7 for 4 h. sIgM levels were detected by qPCR (A, B). C A heat map shows the gene expression profiles of BP7-treated WEHI-231 cells. D The histogram presents differentially expressed genes. E The differentially expressed genes in WEHI-231 cells were validated. Data represent the mean ± standard deviation (s.d.). Significant differences between groups were determined using Student’s t-test, where p < 0.05 is indicated by an asterisk (*).
Figure 4
Figure 4
Pathway interaction network and significant GO terms with a p value within TOP30 in WEHI-231 cells treated with BP7. A The pathway network analysis of 13 significantly enriched pathways (shown in Additional file 5) and B summarized significant GO terms with a p value within TOP30.
Figure 5
Figure 5
BP7 induced autophagy and enhanced AMPK-ULK1 phosphorylation and BCL-2 expression in WEHI-231 cells. A Transmission electron microscopy of autophagosome formation in WEHI-231 cells treated with 10 μg/mL BP7. The arrow indicates autophagosomes in WEHI-231 cells. B LC3 protein expression. C AMPK-ULK1 phosphorylation. D Expression levels of BCL-2. In B and C, WEHI-231 cells treated with 10 μg/mL BSA were used as the irrelevant control (Control), and those treated with rapamycin were used as the positive control. In D, WEHI-231 cells treated with 10 μg/mL BSA were used as the irrelevant control (Control), and those treated with Dox were used as the positive control. Representative Western blots are shown.
Figure 6
Figure 6
Inducing roles of BP7 in a chicken immunization model. Chickens were immunized twice with BP7 and an AIV H9N2 antigen. A HI antibody levels. B IL-4 and IFN-γ cytokine production. C Lymphocyte viability. Data represent the mean ± standard deviation (s.d.). Significant differences between groups were determined using Student’s t-test, where p < 0.05 is indicated by an asterisk (*).
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