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

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.