Distinct signaling requirements for Dμ 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 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.