Defective development of follicular, marginal zone and B1 B cells in interferon regulatory factor 4 deficient mice (B4)

Abstract

Abstract Interferon regulatory factor 4 (IRF4) is an immune system specific transcription factor. Previous studies have demonstrated that IRF4 and its closest relative IRF8 control light chain locus activation and are critical in the pre-B cell development. In this report, the role of IRF4 in the development of follicular, marginal and B1 B cells was further investigated. Our results show that the number of follicular B cells is significantly reduced while the marginal zone and B1 B cell population are dramatically increased in the IRF4 deficient mice. Transplantation study supports a B cell intrinsic role of IRF4 in regulating FO and MZ B cell development. Kinetic study reveals that the distorted FO and MZ B cell development in the absence of IRF4 is a result of accelerated MZ B cell production and reduced FO B cell generation. Molecular analysis further reveals that transitional B cells deficient in IRF4 express lower level of Bcl2. Ectopic expression of a Bcl2 transgene partially restore the normal development of follicular and marginal zone B cells in the IRF4 deficient mice. Thus, IRF4 maybe a novel transcriptional regulator of follicular, marginal zone and B1 B cell development and homeostasis.