FosB Plays A Critical Role in Marginal Zone B Cells Development and BCR-Induced MAPK Activation（英文）

摘要

Objective:FBJ Murine Osteosarcoma Viral Oncogene Homolog B (FosB) is a member of the Fos gene family and plays an important role in transcriptional activation and tumor transformation.Recent studies have shown that the dysregulation of FosB expression is associated with the pathogenesis of a variety of lymphomas.However,the role of FosB in lymphocyte generation and function is still unclear.Methods:In this study,the expression level of FosB mRNA during B cell development was first detected.we generated FosB-knockout(KO) mice and bone marrow (BM) chimeric mice in which FosB is deleted in all of mature B cells.Study on the role of FosB in B cell hematopoietic reconstruction through competitive bone marrow transplantation experiments.We also studied the effects of FosB on B cell proliferation,differentiation,function,and MAPK pathway after BCR induced activation by purifying mature B cells from the spleen.Results:We discovered that FosB deficiency in mice barely affected early development of B cells but markedly reduced marginal zone (MZ) B cells in the spleen.Studies of BM chimeric mice also demonstrated that FosB is required in a cell-intrinsic manner to maintain normal MZ B-cell development.Moreover,FosB deficiency reduced BCR-induced B cell proliferation and survival.FosB deficiency also result in significant changes in basal antibody levels and B cell antibody responses.Furthermore,FosB deficiency specifically impaired Notch2pathway and BCR-induced activation of the MAPK pathway in mature B cells,respectively.Conclusion:FosB plays a critical and distinct role in mature B-cell immune response and development of MZ B cells.

关键词

FosB / MZ B cell / immune response / MAPK / Notch2