PreB cells are moving on

Abstract

In this issue of JEM, Fistonich et al. (https://doi.org/10.1084/jem.20180778) address how the bone marrow microenvironment supports diverse lineages through multiple developmental stages. Differential motility between pro- and preB cells results in differential IL-7 exposure, and, intriguingly, stromal cells respond to abnormal B cells by reducing Il7.

Insights from Dhaval Dixit and Susan R. Schwab.

Model of pro- and preB cell behavior. Left: IL-7 secreted by IL-7^hiCXCL12^hi stromal cells activates IL-7 receptor signaling in proB cells, which strengthens proB cell adhesion to IL-7^hiCXCL12^hi cells by increasing CXCR4 and α4β1 integrin activity. This positive feedback loop results in relatively stationary proB cells. PreBCR signaling breaks the cycle by further increasing CXCR4 activity and decreasing α4β1 integrin–mediated adhesion. As a result, preB cells are more motile and have lower exposure to IL-7. Changes in expression of focal adhesion kinase (FAK) between the pro- and preB cell stages are particularly prominent. Right: In the presence of preB cells with unrepaired double-stranded DNA (dsDNA) breaks, IL-7^hiCXCL12^hi cells decrease expression of Il7 via an unknown mechanism.