Characterization of Lamprey BAFF -like Gene: Evolutionary Implications

Most ligands and receptors from the tumor necrosis factor (TNF) superfamily play very important roles in the immune system. In particular, many of these molecules are essential in the regulation of B cell biology and B cell-mediated immune responses. Hence, in mammals, it is known that many TNF family members play a key role on B cell development, maturation, homeostasis, activation, and differentiation, also influencing the ability of B cells to present antigens or act as regulators of immune responses. Evolutionarily, jawed fish (including cartilaginous and bony fish) constitute the first animal group in which an adaptive immune response based on B cells and immunoglobulins is present. However, until recently, not much was known about the expression of TNF ligands and receptors in these species. The sequences of many members of the TNF superfamily have been recently identified in different species of jawed fish, thus allowing posterior analysis on the role that these ligands and receptors have on B cell functionality. In this review, we summarize the current knowledge on the impact that the TNF family members have in different aspects of B cell functionality in fish, also providing an in depth comparison with functional aspects of TNF members in mammals, that will permit a further understanding of how B cell functionality is regulated in these distant animal groups.

Section: Baff- and April-like Molecule (Balm)mentioning

confidence: 95%

Section: A Proliferation-inducing Ligandmentioning

confidence: 99%

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

Tafalla¹,

Granja²

2018

“…( 17 )], only a few APRIL homolog sequences have been found in teleost, specifically in zebrafish ( Danio rerio ) ( 18 , 19 ), channel catfish ( Ictalurus punctatus ) ( 18 ), Atlantic salmon ( Salmo salar ) ( 18 ), rainbow trout ( Oncorhynchus mykiss ) ( 18 ), and grass carp ( Ctenopharyngodon idella ) ( 20 ). Interestingly, while BAFF is present in all vertebrates, APRIL is missing in cartilaginous fish, birds and several bony fish, suggesting that in some animal groups BAFF might have functionally compensated the loss of APRIL ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of IgM+ B Cell Activities by Rainbow Trout APRIL Reveals Specific Effects of This Cytokine in Lower Vertebrates

Soleto¹,

Morel²,

Martin³

et al. 2018

Tumor necrosis factor ligand superfamily members such as B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been identified in mammals as key regulators of B cell homeostasis and activation. However, the immune functions of APRIL are not as well defined as those of BAFF. Furthermore, while BAFF is present in all vertebrates, APRIL is missing in some animal groups, suggesting that BAFF has compensated the functions of APRIL in these species. In this context, we thought of great interest to explore the effects of APRIL on teleost B cells, given that APRIL appears for the first time in evolution in bony fish. Thus, in this study, we have performed an extensive analysis of the effect of APRIL on B cells using rainbow trout (Oncorhynchus mykiss) as a model species. Our results demonstrate that APRIL induces a specific proliferation of IgM+ B cells by itself and increases IgM secretion without promoting a terminal differentiation to plasma cells. APRIL also increased the levels of surface MHC II and augmented the capacity of these cells to process antigen, effects that were exclusively exerted on IgM+ B cells. Although our results point to a highly conserved role of APRIL on B cell homeostasis and activation throughout evolution, some specific differential effects have been observed in fish in comparison to the effects of APRIL previously described in mammals. Finally, the effects that APRIL induces on rainbow trout IgM+ B cells described in this paper have been compared with those previously reported in response to BAFF.

“…Animals were sacrificed in 0.01% MS-222 followed by exsanguination. Adult lamprey blood was collected by cutting the tail, and leukocytes were separated by Ficoll-Paque gradient centrifugation of the blood with lymphocyte separating solution (160 × g, 20 min) (27)(28)(29). Subsequently, the lamprey lymphocytes were collected for the following studies.…”

Section: Animal Maintenancementioning

confidence: 99%

“…qPCR was performed in triplicate using a TaKaRa PCR Thermal Cycler Dice Real Time System, and L-gapdh (GenBank accession No. KU041137.1) was used as an internal control (28,29,34). The reaction efficiency was tested by the gradual dilution of cDNA template (1x, 5x, 10x, 20x, and 40x).…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Comprehensive Evolutionary Analysis of Lamprey TNFR-Associated Factors (TRAFs) and Receptor-Interacting Protein Kinase (RIPKs) and Insights Into the Functional Characterization of TRAF3/6 and RIPK1

Hou

Pang

2020

TNFR-associated factors (TRAFs) and receptor-interacting protein kinases (RIPKs) are important immunological linker molecules in mammals and play important roles in the TNFα, TLR and IFN signaling pathways. However, the evolutionary origins of these genes in vertebrates have not previously been described in lampreys. In this study, we searched the genomes of Lampetra japonicum, Lethenteron reissneri, and Petromyzon marinus for genes encoding trafs and ripks and performed homologous sequence alignment, phylogenetic tree, functional domain, conserved motif, gene structure, and synteny analyses to determine their evolutionary relationships. The distribution of the lamprey traf and ripk families and the immune response of the gene families in lampreys stimulated by different pathogens were also demonstrated, suggesting a role of structural changes in expression and functional diversification. Additionally, the dual luciferase reporter gene assay showed that the addition of exogenous immunomodulator (TNFα or IFN) to the overexpression of LjLRIPK1a or LjTRAF3/6 significantly downregulated NF-κB or ISRE activation. LjRIPK1a can significantly enhance caspase-8 activity, and overexpression of LjRIPK1a or LjTRAF3a/6 in HEK293T cells results in cell apoptosis. In summary, this study makes an important contribution to the understanding of the traf and ripk gene families in different vertebrates. Our results also provide new evidence for the evolution of vertebrate TRAFs and RIPKs and their impacts on immune regulation.