Role of IRF4 in regulating B cells development in mice

Abstract

Interferon regulatory factor (IRF) family is a broadly expressed group of transcription factors that identified can be stimulated by type I interferon (IFN), among which IRF4, one of the members of IRF family, is widely expressed in immune system. In this project, using IRF-4 deficient (KO) mice, I have characterized B cell development and maturation in the immune system of these mice. To study which stages that B cell development was impaired, both cellularity and phenotypic analysis of B cell subpopulations in various lymphoid organs and body fluid, i.e. bone marrow, peritoneal cavity, blood, spleen, mediastinal lymph node and thymus from IRF-4KO mice and control mice were examined flow cytometry. To examine B cell development at various stages, B220+CD43+IgM- was used for progenitor B cells, B220+CD43-IgM- for precursor B cells and B220+CD43-IgM+ for immature B cells; In peritoneal cavity: B220+CD11b+ for B1 cells, B220+CD11b- for B2 cells, B220+CD11b+CD5+ for B1a cells and B220+CD11b+CD5- for B1b cells; for blood: CD19+ for B cells; CD4+ for CD4-T cells and CD8+ for CD8-T cells; for spleen and lymph node: IgMhi/IgDlo/CD19+ for follical mantle cells, IgMlo/IgDhi/CD19+ for T1 cells, IgMhi/IgDhi/CD19+ for T2 cells, CD21hiCD23-CD19+ for marginal zone B cells, CD21modCD23+CD19+ for follicular B cells, CD138+CD19- for plasma cell, CD138+CD19+ for plasma-blast cell, CD19+CD27+ for memory B cell and CD19+GL7+CD95+ for germinal center B cell, CD19+CD4+ for CD4-T cell and CD19+CD8+ for CD8-T cell; for thymus: CD4+CD3+ for T helper cell, CD8+CD3+ for T cytotoxic cell and CD4+CD8+CD3+ for immature T cell. In IRF-4KO mice, IgM + immature B cells in the bone marrow and CD19+ CD138+ plasma cells in the spleen were significantly reduced. Notably, CD11b+CD5+ B1 cells in the peritoneal cavity were also reduced. However, T cell development in the thymus was not affected. Together, these results have demonstrated that IRF-4 plays a role during B cell developmental process in bone marrow and plasma cell formation in the peripheral lymphoid organs while IRF-4 is not required for T cell development.