Teleost B cell-activating factor (BAFF) diferentially regulates B cell activity in lymphoid and mucosal tissues

Abstract

In mammals, B cell activating factor (BAFF) is a cytokine belonging to the tumor necrosis factor (TNF) family mainly produced by innate immune cells, such as macrophages and dendritic cells, to orchestrate early T-independent B cell responses before T-dependent follicular responses are mounted. Mammalian BAFF can signal through three different receptors: B cell maturation antigen (BCMA), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R). In this context, we have undertaken an exhaustive characterization of the effects of BAFF on rainbow trout (Oncorhynchus mykiss) B cells, since understanding how BAFF regulates B cell responses is of high importance in teleost fish lacking lymphoid follicles. Here, we show that recombinant rainbow trout BAFF strongly promoted the survival of resting unstimulated B cells in vitro without inducing B cell proliferation. In addition, rainbow trout BAFF modulated the levels of membrane MHC class II on B cells as well as the expression of class II-associated genes and immunoglobulins, significantly altering their phenotype. Interestingly, the effects that BAFF produced on B cells were significantly different on B cells from central lymphoid organs (spleen) or mucosal tissues (gills), suggesting the involvement of different BAFF receptors according to the location of B cells. Unravelling the mechanisms underlying the effect of teleost BAFF on B cell differentiation will be of great importance to understand T cell-independent responses and to generate effective adjuvants in future vaccination strategies.