Identification of IFN-γ-producing innate B cells

• DOI: 10.1038/cr.2013.155
• Publication Date: 2013-12-03T11:34:32Z
• Authors: Yan Bao; Xingguang Liu; Chaofeng Han; Sheng Xu; Bin Xie; Qian Zhang; Yan Gu; Jin Hou; Li Qian; Cheng Qian; Huanxing Han; Xuetao Cao
• Keywords: Mice, Knockout; 0301 basic medicine; B-Lymphocytes; CD40 Ligand; Receptors, IgG; NF-kappa B; Bone Marrow Cells; Dendritic Cells; Protein-Tyrosine Kinases; Listeria monocytogenes; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; Agammaglobulinaemia Tyrosine Kinase; Animals; Original Article; CD11a Antigen; CD40 Antigens; Cells, Cultured

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 further investigated. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus and Toll-like receptor ligands, we identified an inducible CD11a(hi)FcγRIII(hi) B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of the immune response. This subpopulation of B cells can promote macrophage activation via generating 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 these innate B cells from the follicular B cells via CD40L-CD40 ligation. Increased Bruton's tyrosine kinase activation was found to be responsible for the increased activation of non-canonical NF-κB pathway in these 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.