Abstract
B cell activating factor (BAFF) is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF) from the teleost fish tongue sole (Cynoglossus semilaevis). CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF) bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.
Highlights
B-cell activating factor (BAFF), known as BLys, TALL-1, THANK, zTNF4, and TNFSF13b, is a member of the tumor necrosis factor (TNF) family, and is mainly produced by PLOS ONE | DOI:10.1371/journal.pone.0136015 August 21, 2015A Teleost BAFF Promotes Innate and Adaptive Immunity innate immune cells, such as neutrophils, monocytes, and dendritic cells (DCs), as well as activated T cells and malignant B cells [1,2,3,4,5,6,7]
transmembrane activator and CAML interactor (TACI) and B-cell maturation antigen (BCMA) can bind to a proliferation-inducing ligand (APRIL), another member of the TNF family that shares a high level of sequence similarity with BAFF [10,11], while BAFF-R is specific for BAFF
CsBAFF consists of 261 amino acid residues and contains a conserved domain typical of the TNF superfamily, which is formed by residues 112–260
Summary
B-cell activating factor (BAFF), known as BLys, TALL-1, THANK, zTNF4, and TNFSF13b, is a member of the tumor necrosis factor (TNF) family, and is mainly produced by PLOS ONE | DOI:10.1371/journal.pone.0136015 August 21, 2015A Teleost BAFF Promotes Innate and Adaptive Immunity innate immune cells, such as neutrophils, monocytes, and dendritic cells (DCs), as well as activated T cells and malignant B cells [1,2,3,4,5,6,7]. B-cell activating factor (BAFF), known as BLys, TALL-1, THANK, zTNF4, and TNFSF13b, is a member of the tumor necrosis factor (TNF) family, and is mainly produced by PLOS ONE | DOI:10.1371/journal.pone.0136015. BAFF exerts its function by interaction with its receptor. Three BAFF binding receptors have been identified, i.e., transmembrane activator and CAML interactor (TACI), B-cell maturation antigen (BCMA), and BAFF-R [8,9]. TACI and BCMA can bind to a proliferation-inducing ligand (APRIL), another member of the TNF family that shares a high level of sequence similarity with BAFF [10,11], while BAFF-R is specific for BAFF. Recent studies suggest that BAFF-R may be the principal receptor responsible for B-cell development and survival [9]
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