title: Kras Is Critical for B Cell Lymphopoiesis.
abstract: The three major Ras members, Kras, Hras, and Nras, are highly homologous and individual Ras genes can have distinct biological functions. Embryonic lethality of Kras-deficient mice precludes study of the biological functions of this Ras family member. In this study, we generated and examined mice with hematopoietic-specific deletion of Kras and bone marrow (BM) chimeric mice with B cell-specific targeted deletion of Kras. Hematopoietic-specific deletion of Kras impaired early B cell development at the pre-B cell stage and late B cell maturation, resulting in the reduction of BM pre-, immature, and mature B cells and peripheral follicular, marginal zone, and B1 mature B cells. In contrast, Kras deficiency did not affect T cell development. Studies of BM chimeric mice with B cell-specific deletion of Kras demonstrated that Kras deficiency intrinsically impaired B cell development. Kras deficiency reduced BCR-induced B cell proliferation and survival. Furthermore, Kras deficiency specifically impaired pre-BCR- and BCR-induced activation of the Raf-1/MEK/ERK pathway in pre-B and mature B cells, respectively. Thus, Kras is the unique Ras family member that plays a critical role in early B cell development and late B cell maturation through controlling the Raf-1/MEK/ERK pathway.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53792;
authors.forename: Xiaona
authors.identifier: http://orcid.org/0000-0001-9996-1466
authors.initials: X
authors.lastname: You
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Guoping
authors.initials: G
authors.lastname: Fu
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226; Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China;
authors.forename: Xinlin
authors.initials: X
authors.lastname: Su
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226; Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People's Republic of China; and.
authors.forename: Fen
authors.identifier: http://orcid.org/0000-0002-8575-4834
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China;
authors.forename: Zhihong
authors.identifier: http://orcid.org/0000-0002-1902-4198
authors.initials: Z
authors.lastname: Wu
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53792;
authors.forename: Jing
authors.identifier: http://orcid.org/0000-0003-1194-0666
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
authors.forename: Renren
authors.identifier: http://orcid.org/0000-0003-2420-8212
authors.initials: R
authors.lastname: Wen
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226 demin.wang@bcw.edu.
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)