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

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.

What goes around comes around: an investigation of resistance to proliferative kidney disease in rainbow trout Oncorhynchus mykiss (Walbaum) following experimental re‐exposure

“…; Meng, Sun & Xu ). However, a vaccination study of tongue sole Cynoglossus semilaevis (Günther) suggested that BAFF enhanced the immunoprotection primed by a DNA vaccine and augmented the production of antibodies (Sun & Sun ). However, in the present study, BAFF expression levels in the first infection and reinfection group did not constitute any trends with IgM sec expression in the posterior kidney or of IgM+ B cells in the blood.…”

Novel Insights on the Regulation of B Cell Functionality by Members of the Tumor Necrosis Factor Superfamily in Jawed Fish

“…The homologue sequences to mammalian BAFF have been reported in many teleost fish species including rainbow trout ( 41 ), zebrafish ( 120 ), mefugu ( Takifugu obscurus ) ( 121 ), Japanese sea perch ( Lateolabrax japonicus ) ( 122 ), grass carp ( Ctenopharyngodon idella ) ( 123 ), yellow grouper ( Epinephelus awoara ) ( 124 ), miiuy croaker ( Miichthys miiuy ) ( 125 ), tongue sole ( Cynoglossus semilaevis ) ( 126 ), Nile tilapia ( Oreochromis niloticus ) ( 127 ), rock bream ( Oplegnathus fasciatus ) ( 128 ), and also in cartilaginous fish such as white-spotted catshark ( Chiloscyllium plagiosum ) ( 129 ), spiny dogfish ( Squalus acanthias ) ( 130 ), and small-spotted catshark ( Scyliorhinus canicula ) ( 131 ) (summarized in Table 3 ). Interestingly, some studies have revealed that many cartilaginous and bony fish species have more than one BAFF gene ( 51 , 54 ), representing two distinct groups.…”

“…Recombinant BAFF proteins have been generated in some of these fish species, such as, for example, the cartilaginous fish white-spotted catshark ( 129 ), and the teleost zebrafish ( 120 ), fugu ( 121 ), Japanese sea perch ( 122 ), yellow grouper ( 124 ), tongue sole ( 126 ), rock bream ( 128 ), or tilapia ( 127 ), to carry out functional studies. These studies have proven an increase on the number of leukocytes mediated by BAFF, although the authors did not clarify whether this was due to a promotion of cell survival or an increase on cell proliferation, and they did not demonstrate if the surviving/proliferating fish leukocytes were in fact B cells.…”

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

“…Briefly, a PoPTEN specific siRNA (5′-GCACTTCAACATCCGTCAC-3′) was inserted into the siRNA expression vector pRNAT-CMV3.1 (GenScript, Piscataway, NJ, USA) at BamH I/Alf II restriction sites, resulting in plasmid pPoPTENsi. The inhibitory effect of pPoPTENsi on PoPTEN expression in flounder tissues was verified by qRT-PCR as reported previously [ 102 ]. The negative control plasmid, pPoPTENsiC, which expresses a scramble siRNA (5′-ACCTACTGCGCTTAACACC-3′), was similarly constructed.…”

“…The PCR product was ligated into pCN3 [ 101 ] at the EcoR V site, resulting in pPoPTEN. The plasmid pPoPTENsi used for the knockdown of PoPTEN was constructed by using siRNA as reported previously [ 102 ]. Briefly, a PoPTEN specific siRNA (5′-GCACTTCAACATCCGTCAC-3′) was inserted into the siRNA expression vector pRNAT-CMV3.1 (GenScript, Piscataway, NJ, USA) at BamH I/Alf II restriction sites, resulting in plasmid pPoPTENsi.…”