CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity

Abstract

<div><p>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 <i>in vivo</i> conditions, is essentially unknown. In this study, we conducted <i>in vivo</i> as well as <i>in vitro</i> functional analyses of a BAFF homologue (CsBAFF) from the teleost fish tongue sole (<i>Cynoglossus semilaevis</i>). CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. <i>CsBAFF</i> 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 <i>in vivo</i> study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of <i>CsBAFF</i> 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 <i>in vivo</i> evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.</p></div