Mechanisms of selection mediated by interleukin‐7, the preBCR, and hemokinin‐1 during B‐cell development

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Abstract
Summary:  Many of the stromal‐derived signals and factors that regulate B lymphopoiesis have been identified. We review recent evidence from our laboratory that shows that there are at least three phases during B‐cell development when cells direct their own maturation, independent of stromal cells. Following the expression of the preB‐cell receptor (preBCR), cells acquire the ability to proliferate in low levels of interleukin‐7 (IL‐7), which acts as a self‐selecting mechanism to expand cells that have successfully expressed a preBCR in environments that are non‐permissive to preBCR– cells. Second, the preBCR is required for a contact‐mediated event between B‐cell progenitors. Disruption at this stage prevents the further maturation of progenitors to the lipopolysaccharide (LPS)‐responsive stage. Finally, the transition from IL‐7 receptor to mature antigen receptor‐based signaling is enhanced by a novel member of the tachykinin family, hemokinin‐1. This series of maturation, survival, and differentiation signals is generated by B‐lineage cells as they progress through developmental checkpoints on the way to becoming functionally mature cells.