The Ancient Cytokine BAFF- and APRIL-like Molecule Regulates the Functionality of Teleost IgM+ B Cells Similarly to BAFF and APRIL

TNF superfamily (TNFSF) members, such as BAFF and a proliferation-inducing ligand (APRIL), emerged in vertebrates as key regulators of B cell homeostasis and activation. Many cartilaginous and teleost fish contain an additional gene, designated as BAFF- and APRIL-like molecule (BALM), of unknown function and lost in tetrapods. In this study, we have performed a wide characterization of the functions of BALM on naive B cells for the first time, to our knowledge, in teleosts using rainbow trout ( Oncorhynchus mykiss ) as a model. Similar to BAFF and APRIL, BALM increased the survival and promoted the proliferation of peripheral blood IgM + B cells and cooperated with BCR cross-linking to increase the proliferation rate of IgM + B cells. BALM also seemed to be a differentiating factor for trout IgM + B cells, as it increased IgM secretion and increased cell size. Additionally, BALM appeared to increase the Ag-presenting properties of IgM + B cells, augmenting MHC class II surface expression and upregulating the phagocytic capacity of these cells. Finally, the fact that there was no synergy between BALM and BAFF/APRIL in any of these functions strongly suggests that BALM signals through the same receptors as BAFF and APRIL to carry out its functions. This hypothesis was further supported in competitive BALM binding assays. The results presented provide relevant information for understanding how these TNFSF members cooperate in teleost fish to regulate B cell functionality, helping us to interpret the evolutionary relations between molecules of this family.