Transcriptome analysis in primary B lymphoid precursors following induction of the pre-B cell receptor

Abstract

Pre-BCR signals are part of a checkpoint where early precursor (pre-) B cells with a pairing Ig muH chain (muHC) are clonally expanded before they differentiate into IgL-rearranging, resting pre-B cells. A pre-BCR consists of two muHCs, two surrogate L chains and the signal transducer Igalpha/Igbeta. The molecular circuits by which the pre-BCR controls proliferation and differentiation of pre-B cells are poorly characterized. Therefore, we identified the differential transcriptome by genome-wide expression profiling in progenitor (pro-) B cells from a Rag2-deficient mouse, in which the expression of a transgenic muHC and thus a pre-BCR as well as pre-BCR-mediated clonal expansion can be controlled by tetracycline (muHC-inducible mouse). This analysis revealed that pre-BCR signals upregulate components of the BCR signalosome, open the IgL chain (LC) locus and induce the krüppel-like transcription factor KLF2, a key regulator of quiescence and lymphocyte migration. Hence, pre-BCR signals establish the molecular network for BCR signaling even before the production of an IgLC and induce the expression of KLF2, a candidate for controlling clonal expansion and migration of functional pre-B cells.