B-Lymphopoiesis in Fetal Liver, Guided by Chemokines.

Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium. Once inside fetal liver, the progenitors are attracted by the chemokine CXCL12 to ALCAM+ liver mesenchyme, which produces not only this chemokine, but also the myeloid differentiation-inducing cytokine CSF-1 and the lymphoid differentiation-inducing cytokine IL7. In this mesenchymal environment B-lymphocyte lineage progenitors are then induced by IL7 to enter differentiation and Ig gene rearrangements. Within 3-4 days surface IgM+ immature B-cells develop, which are destined to enter the B1-cell compartments in the peripheral lymphoid organs.