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Rap signaling is crucial for the competence of IL-7 response and the development of B-lineage cells.

Abstract：

:Rap family GTPases consist of multiple members with substantial functional redundancy. With the use of transgenic mice conditionally expressing a bona fide dominant-negative Rap1 mutant, Rap1A17, capable of inhibiting the activation of all Rap family members in B-lineage cells (mb.1-Rap1A17 Tg), we demonstrate that these mice show a defective generation of pre-B cells in bone marrow, resulting in a significant diminution of peripheral mainstream B cells. The effect is attributed to the impaired survival and expansion of B-lineage progenitors in response to IL-7, despite normal IL-7Ralpha expression. The pre-B cells from mb.1-Rap1A17 Tg mice showed a significantly reduced expression of c-myc and E2A, and the competence of IL-7 response was restored by the transduction of c-myc, but not by constitutively active (CA) Stat5a, CA PI3K-p100, or bcl-2. The residual follicular B cells with complete Cre-mediated recombination proliferated normally in response to B-cell receptor stimulation and showed efficient germinal center reaction in vivo. These results show that endogenous Rap signaling plays a crucial role selectively in B-lineage cell development by sustaining the competence for IL-7 response, whereas it is dispensable for mature B-cell function.

journal_name

Blood

journal_title

Blood

authors

Katayama Y,Sekai M,Hattori M,Miyoshi I,Hamazaki Y,Minato N

doi

10.1182/blood-2009-03-213371

subject

Has Abstract

pub_date

2009-08-27 00:00:00

pages

1768-75

issue

9

eissn

0006-4971

issn

1528-0020

pii

blood-2009-03-213371

journal_volume

114

pub_type

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