NDLI: Ras Mediates Effector Pathways Responsible for Pre-B Cell Survival, Which Is Essential for the Developmental Progression to the Late Pre-B Cell Stage

Content Provider	PubMed Central
Author	Nagaoka, Hitoshi Takahashi, Yoshimasa Hayashi, Reiko Nakamura, Tohru Ishii, Kumiko Matsuda, Junichiro Ogura, Atsuo Shirakata, Yumiko Hajime, Karasuyama Sudo, Tetsuo Nishikawa, Shin-ichi Tsubata, Takeshi Mizuochi, Tsuguo Asano, Toshihiko Sakano, Hitoshi Takemori, Toshitada
Copyright Year	2000
Abstract	Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21 ras in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21Asn-17 Ha-ras was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21 ras activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21 ras activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21 ras mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.
Starting Page	171
File Format	PDF
ISSN	15409538
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	2
Volume Number	192
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2000-07-17
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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