LYMPHOHEMATOPOIETIC RECONSTITUTION USING WHEAT-GERM AGGLUTININ-POSITIVE HEMATOPOIETIC STEM-CELL TRANSPLANTATION WITHIN BUT NOT ACROSS THE MAJOR HISTOCOMPATIBILITY ANTIGEN BARRIERS

Nonadherent (NA), low density (LD), wheat germ agglutinin-positive (WGA+) murine hemopoietic stem cell-enriched preparations (HSCPs) were tested for the capability to reconstitute lymphohemopoietic elements in lethally irradiated mice. HSCPs from BALB/c mice reconstituted lethally irradiated, major histocompatibility complex (MHC)-matched DBA/2 mice to normal histology of the thymus and spleen and normal humoral and cellular immune functions. By contrast, lethally irradiated B6 mice could not be reconstituted after transplantation with NA, LD, WGA+ cells from MHC-mismatched BALB/c mice. We previously observed frequent survival, stable chimerism, and normally vigorous functioning immune systems in B6 mice transplanted with T-cell-depleted bone marrow from both BALB/c and B6 donors. To extend these findings to a stem cell transplantation system, lethally irradiated B6 mice were transplanted with NA, LD, WGA+ cells from both BALB/c and B6 mice. These mixed stem cell-enriched preparations did not reconstitute the lethally irradiated, MHC-mismatched mice. By contrast, such HSCPs from BALB/c plus DBA/2 into DBA/2 mice reconstituted the hematologic and lymphoid tissues and functional immune systems when the donor and the recipient pairs were matched at MHC and mismatched at multiminor histocompatibility barriers. These purified blood progenitors thus appear to lack certain cells/factors essential for engraftment and reconstituting recipients in a fully allogeneic environment.