TY - JOUR
T1 - Distinct signaling requirements for Dμ selection, IgH allelic exclusion, Pre-B cell transition, and tumor suppression in B cell progenitors
AU - Hayashi, Katsuhiko
AU - Yamamoto, Mutsumi
AU - Nojima, Takuya
AU - Goitsuka, Ryo
AU - Kitamura, Daisuke
N1 - Funding Information:
We are grateful to Drs. H. Karasuyama for antibody, Y. Hara for the cell sorting, and K. Rajewsky and T. Kaisho for providing CD19-deficient mice. This work was supported by grants to D.K., R.G., and K.H. from the Ministry of Education, Science, Sports and Culture in Japan and Japan Society for Promotion of Science.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - The pre-B cell receptor triggers expansion and differentiation of pre-B cells (the pre-B cell transition), as well as inhibition of VH to DJH recombination (allelic exclusion). The latter also accounts for counter-selection of pro-B cells expressing Dμ protein (Dμ selection). However, the signaling pathways responsible for these events remain poorly defined. Here we show complete arrest of B cell development at the pre-B cell transition in BASH/CD19 double mutant mice, indicating partial redundancy of the two B cell-specific adaptors. Allelic exclusion remained intact in the double mutant mice, whereas Dμ selection was abolished in BASH mutant mice. Thus, distinct signals are required for these events. In addition, both mutant mice succumbed to pre-B cell leukemia, indicating that BASH and CD19 contribute to tumor suppression.
AB - The pre-B cell receptor triggers expansion and differentiation of pre-B cells (the pre-B cell transition), as well as inhibition of VH to DJH recombination (allelic exclusion). The latter also accounts for counter-selection of pro-B cells expressing Dμ protein (Dμ selection). However, the signaling pathways responsible for these events remain poorly defined. Here we show complete arrest of B cell development at the pre-B cell transition in BASH/CD19 double mutant mice, indicating partial redundancy of the two B cell-specific adaptors. Allelic exclusion remained intact in the double mutant mice, whereas Dμ selection was abolished in BASH mutant mice. Thus, distinct signals are required for these events. In addition, both mutant mice succumbed to pre-B cell leukemia, indicating that BASH and CD19 contribute to tumor suppression.
UR - http://www.scopus.com/inward/record.url?scp=0037805640&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037805640&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(03)00142-0
DO - 10.1016/S1074-7613(03)00142-0
M3 - Article
C2 - 12818163
AN - SCOPUS:0037805640
SN - 1074-7613
VL - 18
SP - 825
EP - 836
JO - Immunity
JF - Immunity
IS - 6
ER -