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. 2020 Oct 8;10:592205. doi: 10.3389/fonc.2020.592205

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Copyright © 2020 Haselager, Kater and Eldering

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Spectrum of circulating CLL cells illustrating the proliferative fraction enriched in LN emigrants versus the resting fraction enriched in LN immigrants. CXCR4high/CD5low cells are in a resting state. When these cells are activated in the LN, CD5 is upregulated and CXCR4 is internalized. These CXCR4low/CD5high cells are released from the LN and migrate into the PB. Eventually these cells become more quiescent leading to downregulation of CD5 and renewed surface expression of CXCR4 which increases the likelihood of a return to the LN.