Kras Is Critical for B Cell Lymphopoiesis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yuhong ChenDemin Wang

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 ...Continue Reading

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Citations

Dec 25, 2019·The Journal of Experimental Medicine·Natalia DavidzohnZiv Shulman
Mar 15, 2016·Stem Cells·Alisa DamnernsawadJing Zhang
Mar 4, 2020·FASEB BioAdvances·Noriko YokoyamaKazuhisa Iwabuchi
Nov 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lan LuoDemin Wang

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