In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 4 ( 2016-02-15), p. 1678-1685
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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1502112
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
Permalink
