Summary of a hypothetical model of B cell TEM according to EphA2-EFNA4 interaction and its regulation by EFNA4 signaling strength. Low levels of EFNA4 expression, like those present in most of the normal PB B cells, allow TEM progression to proceed through generating EphA2 forward signals into endothelial cells that connect to the adhesion machinery (at least ICAM-1, VCAM-1 CAMs). By contrast, the greater the levels of EFNA4 expression in B cells, as determined in CLL B cells, led to inhibitory reverse signals that impair TEM.