Recapitulation ofNormalandAbnormalBB RatImmuneSystemDevelopment inscidMouse/RatLymphohemopoietic Chimeras

Micehomozygous forthemutation "severe combined immune deficiency" (C.B17-scid/scid) lack functional TandBlymphocytes andreadily accept tumorxenografts. Partial lymphohemopoietic scid/human andmouse/rat chimeras havebeendescribed, butcomplete chimerization withthymic engftment andgeneration ofdonor-origin thymocytes hasnotbeen achieved. Wenowreport that low-dose irradiation permits the engraftment ofBBratfetal liver stemcells inscid recipients. Weobserved that BBratfetal liver cells inJected into irradiated scid miceestablish arathemopoietic system inthescid mouse bonemarrow andpopulate thescid mousethymus. Thesestem cells generated rat-origin thymocytes thatmigrated tothescid mousespleen, aperipheral lymphoid organ. Finally, wefound that xenogeneic chimeras created using fetal liver cells fromthe abnormal (lymphopenic, diabetes prone) subline ofBBrats recapitulated boththequantitative andphenotypic abnormalities ofthedonor rat. Xenogeneic lymphohemopoietic chimeras established inscid micemayprovide apowerful newtool inthe study ofimmunesystem development andautoimmunity. (J. Clin. Invest. 1991. 88:717-719.) Keywords: scid mouse -BB/ Worrat *lymphopoiesis - chimera *immunesystem development