Figure 4: Immature B cell egress is predominantly controlled by attenuation of CXCR4 signaling.

ProB cells (magenta) are predominantly non-motile and highly adherent to VCAM-1 expressed on CXCL12^Hi MPCs. These cells express very little amounts of egress-promoting S1P receptor-1 but are highly dependent on CXCR4 signaling for bone marrow retention. PreB cells (purple) are motile (indicated by amoeboid shape with ruffled edges) due to high levels of CXCR4 expression, which also promotes their retention in the bone marrow. PreB also express very little amounts of egress-promoting S1P receptors. Immature B cells (red) gradually reduce CXCR4 expression while S1PR1 expression is markedly increased. Reduced CXCL12-mediated retention of immature B cells, particularly at the IgD^lo B cell stage, causes the cells to exit into the sinusoids. S1P plays a small but detectable role in promoting immature B cell egress into sinusoids. Upon egress, immature B cells are temporarily retained inside sinusoids via a mechanism primarily dependent on CB2-mediated α4β1 transactivation and adhesion to VCAM-1 expressed on luminal sinusoidal endothelium. The CB2 ligand 2-Ag is presumably enriched in the perisinusoidal/intrasinusoidal space.