Kras Is Critical for B Cell Lymphopoiesis. J Immunol 2016 Feb 15;196(4):1678-85
Date
01/17/2016Pubmed ID
26773157Pubmed Central ID
PMC4744498DOI
10.4049/jimmunol.1502112Scopus ID
2-s2.0-84958580592 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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.
Author List
Chen Y, Zheng Y, You X, Yu M, Fu G, Su X, Zhou F, Zhu W, Wu Z, Zhang J, Wen R, Wang DMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Blotting, Western
Cell Differentiation
Cell Proliferation
Electrophoretic Mobility Shift Assay
Flow Cytometry
Lymphocyte Activation
Lymphopoiesis
Mice
Mice, Inbred C57BL
Mice, Transgenic
Precursor Cells, B-Lymphoid
Proto-Oncogene Proteins p21(ras)
Signal Transduction
