The pre-B cell receptor in B cell development: recent advances, persistent questions and conserved mechanisms.

B cell development is a process tightly regulated by the orchestrated signaling of cytokine receptors, the pre-B cell receptor (BCR) and the B cell receptor (BCR). It commences with common lymphoid progenitors (CLP) up-regulating the expression of B cell-related genes and committing to the B cell lineage. Cytokine signaling (IL-7, stem cell factor, FLT3-L) is essential at this stage of development as it suppresses cell death, sustains proliferation and facilitates heavy chain rearrangements. As a result of heavy chain recombination, the pre-BCR is expressed, which then becomes the primary determiner of survival, cell cycle entry and allelic exclusion. In this review, we discuss the mechanisms of B cell lineage commitment and describe the signaling pathways that are initiated by the pre-BCR. Finally, we compare pre-BCR and pre-TCR structure, signal transduction and function, drawing parallels between early pre-B and pre-T cell development.