A semiquantitative assay was developed and used to measure the effects of immune responses against 16 independent non-H-2 antigenic loci on erythropoietic stem cells. The assay compares repopulation in genetically anemic WBB6F1-W/W v recipients that have normal immune responses, and in lethally irradiated WBB6F 1 +/+ mice whose immune responses are suppressed by the irradiation. The differences in repopulating ability between these two types of recipients measure how immune responses affect erythropoietic stem cells. Stem cell repopulating abilities for the cells with antigens specified by the Thy-1, H-l, H-24, Ly-1, H-37, and H-171oci were affected slightly, if at all. Repopulating abilities were moderately reduced by responses against antigens specified by H-15, 16, Ea-2, and Ly-2, 3 loci, and against the differences between the B6 and B10 genotypes, although marrow of these types cured W/W ~ recipients. A surprising result occurred for the antigen specified by the H-8 locus, in which immune responses strongly reduced repopulating abilities, although this type of marrow cell cured W/W v recipients. A comparison of these results with skin graft survival times suggests that the antigens specified by the H-17 and H-24 loci are strongly immunogenic on skin but not on marrow stem cells, while those specified by the H-12 and H-8 loci are strongly immunogenic on marrow stem cells but not on skin. is extremely sensitive because the competition between two cell types to repopulate a recipient magnifies small differences in proliferative capacity (Harrison 1980, 1981, Harrison and Astle 1982).
W-anemic mouse recipients have provided a valuable model for studying marrow antigens because their immune responses are normal (Mekori and Phillips 1969, Harrison andCherry 1975), but they are erythropoietically repopulated by normal marrow grafts that cure the anemia (Russell et al. 1959). Both erythrocytes and granulocytes in cured W/W v recipients become essentially 100 % donor type (Russell and Bernstein 1968, Murphy et al. 1973) and lymphoid tissues are substantially, but not completely repopulated by donor cells (Harrison et al. 1979).
The ability of marrow allografts to cure W-anemic mice is not necessarily related to skin graft survival times (Harrison and Doubleday 1976). Thus antigens may have different levels of immunogenicity in different tissues. A semiquantitative assay is needed to measure the immunogenicity of antigens on erythropoietic stem cells, rather than the all or nothing cure of W/W v recipients. Such an assay is detailed in this report, as are the results using 16 different B6 or B10 congenic lines.