B Cells in Teleost Fish Act as Pivotal Initiating APCs in Priming Adaptive Immunity: An Evolutionary Perspective on the Origin of the B-1 Cell Subset and B7 Molecules

Abstract

The long-held paradigm that B cells cannot uptake nonspecific particulate Ags for the initiation of primary adaptive immunity has been challenged by the recent discovery that teleost B cells have potent phagocytic and microbicidal abilities. This discovery provides preliminary clues that primitive B cells might act as initiating APCs in priming adaptive immunity. In this study, zebrafish B cells clearly showed a potent Ag-presenting ability to both soluble Ags and bacterial particles to prime naive CD4+ T cell activation. This finding demonstrates the innate-like nature of teleost B cells in the interface of innate and adaptive immunity, indicating that they might consist of a major population of initiating APCs whose performance is similar to that of dendritic cells. Given the functional similarities between teleost B cells and the mammalian B-1 subset, we hypothesize that B-1 lineage and teleost B cells might originate from a common ancestor with potent phagocytic and initiating APC capacities. In addition, CD80/86 and CD83 costimulatory signals were identified as being essential for B cell–initiated adaptive immunity. This result suggests that the costimulatory mechanism originated as early as the origin of adaptive immunity and is conserved throughout vertebrate evolution. In fish, only a single CD80/86 copy exists, which is similar to mammalian CD86 rather than to CD80. Thus, CD86 might be a more primordial B7 family member that originated from fish. This study provides valuable insights into the evolutionary history of professional APCs, B cell lineages, and the costimulatory mechanism underlying adaptive immunity as a whole.

Molecular characterization and expression of CD2 in Nile tilapia (Oreochromis niloticus) in response to Streptococcus agalactiae stimulus

“…The BLAST analysis revealed the overall sequence homology of the CD2 proteins among different species, even among different fish species, was very poor. This finding is consistent with the result of previous studies about other costimulatory molecules in teleost, including CD28 [39,40], CD80/ CD86 [41,42] and CTLA-4 [39]. Fish are the most primitive vertebrates to possess essential components of T-cell immunity, which includes MHC, TCRs, CD3, CD4, CD8, etc, to allow the clonal selection of T-cells [27,28].…”

Essential Roles of TIM-1 and TIM-4 Homologs in Adaptive Humoral Immunity in a Zebrafish Model

“…Wild-type AB zebrafish were bred in our laboratory and maintained in circulating water at 28˚C under standard conditions, as previously described (26). One-year-old male and female fish with body lengths of 2-3 cm and weights of 1.0-1.5 g that exhibited healthy appearance and activity were used for the study.…”

“…The anti-DrTIM-1 and anti-DrTIM-4 Abs were affinity purified into IgG by using a protein A-agarose column (Qiagen) and a membrane-based Ag-absorbent protocol as previously described (44,45). Western blot was used to characterize the specificity of the Abs (26). The Abs against D. rerio MHC class II (DrMHC-II), DrIgM, DrCD4, DrCD40, and DrCD154, including mouse anti-DrMHC-II, mouse anti-DrIgM, rabbit anti-DrIgM, mouse anti-DrCD4, rabbit anti-DrCD4, rabbit anti-DrCD40, and rabbit anti-DrCD154, were produced from our previous studies (26,29,46).…”

Characterization of SIGIRR/IL-1R8 Homolog from Zebrafish Provides New Insights into Its Inhibitory Role in Hepatic Inflammation

“…to produce EGFP-tagged infective viruses (38,39). Subsequently, the lentiviruses were packaged and propagated in HEK293T cells via cotransfection of PLB, pCMV-VSVG, and pCMV-dR8.2 using FuGENE HD, followed by concentration via ultracentrifugation.…”

“…Subsequently, the lentiviruses were packaged and propagated in HEK293T cells via cotransfection of PLB, pCMV-VSVG, and pCMV-dR8.2 using FuGENE HD, followed by concentration via ultracentrifugation. The titers of the produced lentiviruses were determined by transduction and flow cytometric analysis of EGFP expression in HEK293T cells (31,39). The silencing efficacy of the lentiviruses (LV4 for DrSIGIRR and LVtrif for DrTRIF) was evaluated in the liver by real-time PCR after the zebrafish were injected with LV4, LVtrif, or LVc (lentivirus harboring scrambled shRNA as negative control) (2 3 10 5 transduction units/fish) once a day for 3 d.…”