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Kras Is Critical for B Cell Lymphopoiesis. J Immunol 2016 Feb 15;196(4):1678-85

Date

01/17/2016

Pubmed ID

26773157

Pubmed Central ID

PMC4744498

DOI

10.4049/jimmunol.1502112

Scopus ID

2-s2.0-84958580592   7 Citations

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.

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 D

Authors

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
B-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
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5