CD34 is required for engraftment of nonlethally irradiated recipients. (A) Schematic of experimental design. 5 × 10⁶ E15 FTLs of each genotype were injected into irradiated W/W^v recipients. wt cells (bearing the CD45.1 allotypic marker) were injected competitively with cd34^−/− or wt (control) cells (CD45.2), and donor-derived (c-kit⁺) BM cells were analyzed for relative contributions 12 weeks after transplantation. (B) CD34 was not required for reconstitution of W/W^v mice pretreated with high-dose irradiation. Error bars represent SD. (C) cd34^−/− cells were at a significant disadvantage in sublethally irradiated W/W^v recipients (combined data from 2 experiments; P = .001). Error bars represent SD. (D) cd34^−/− cells did not contribute to long-term engraftment of nonirradiated wt recipients (P = .001). 10⁷ CD45.2 (wt or cd34^−/−) cells were injected into nonirradiated wt (CD45.1) recipients, and donor-derived cells in peripheral blood were quantitated 12 weeks after transplantation based on CD45.2 expression. Error bars represent SD. (E) Proposed model demonstrating the effect of irradiation on the BM microenvironment and its effect on reconstitution by wt or cd34^−/− cells. Lethal irradiation creates gaps between vascular endothelial cells, which allow extravasation of cells regardless of CD34 expression. In nonirradiated recipients, the vasculature remains intact, and the antiadhesiveness of CD34 enables transmigration. This is blocked in the absence of CD34.