Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors.
The pre-B cell receptor triggers expansion and differentiation of pre-B cells (the pre-B cell transition), as well as inhibition of V(H) to DJ(H) recombination (allelic exclusion). The latter also accounts for counter-selection of pro-B cells expressing Dmu protein (Dmu 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 Dmu 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.
Hayashi
Katsuhiko
K
Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, 278-0022, Chiba, Japan.
Yamamoto
Mutsumi
M
Nojima
Takuya
T
Goitsuka
Ryo
R
Kitamura
Daisuke
D
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D018941:Antigens, CD19; C113939:B cell linker protein; D002352:Carrier Proteins; D007143:Immunoglobulin Heavy Chains; D010750:Phosphoproteins