A novel population of IFN-γ-producing B cells promote innate defense against Listeria monocytogenes infection (INC4P.337)

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Abstract Although B cells play important roles in the humoral immune response and the regulation of adaptive immunity, B cell subpopulations with unique phenotypes, particularly those with non-classical immune functions, should be investigated further. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus, and TLR ligands, we identified an inducible CD11ahiFcγRIIIhi B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of pathogen infection. This subpopulation of B cells can promote macrophage activation via IFN-γ, thereby facilitating the innate immune response against intracellular bacterial infection. As this new subpopulation is of B-cell origin and exhibits the phenotypic characteristics of B cells, we designated these cells as IFN-γ-producing innate B cells. Dendritic cells were essential for the inducible generation of innate B cells from follicular B cells via CD40L-CD40 ligation, and increased Btk activation was found to be responsible for the increased activation of noncanonical NF-κB in innate B cells after CD40 ligation, with the consequent induction of additional IFN-γ production. The identification of this new population of innate B cells may contribute to a better understanding of B cell functions in anti-infection immune responses and immune regulation.