Variation in H-2 antigen expression on lymphomyeloid cells in semi-allogeneic irradiation chimeras

Spleen cells from 30 individual murine irradiation chimeras of the type (P1 X P2)F1----P1 were compared in a rosetting assay for H-2K and H-2D cell surface antigen expression with normal (P1 X P2)F1 hybrid controls. Eleven out of the 30 chimeras were in the normal range, but the other 19 differed from F1 controls by 4- to 100-fold in endpoint titre for at least one H-2K or H-2D antigen. Every possible class of variation was found, i.e. up or down variation of H-2K or H-2D antigens of P1 or P2 type. This evidence, together with data from T6 chromosome marker experiments which also showed full reconstitution of lethally irradiated P1 recipients by (P1 X P2)F1 donor lymphomyeloid stem cells, suggested that incomplete reconstitution was not the cause of H-2 antigenic variation. Low expression of P2 H-2 antigens on spleen cells derived from (P1 X P2)F1----P1 chimeras was investigated further. Fifteen lethally irradiated (P1 X P2)F1 recipients of bone marrow cells from two such chimeras were all of normal F1 H-2 phenotype when tested 10-12 weeks after reconstitution, thus excluding stable, low P2 H-2-expressing variant F1 stem cells as a cause of the phenomenon. If P1 recipients were hyperimmunized against P2 cells before lethal irradiation and reconstitution with (P1 X P2)F1 stem cells, there were significantly fewer Till- McCulloch colonies in their spleens 10 days after reconstitution than in spleens of unimmunized controls. Also greater than 90% of immunized recipients died by 6 weeks after stem cell injection but two survivors both showed very low levels of P2 H-2K and H-2D antigens. These results together with previously published evidence of anti-P2 Tc cell activity and P2 skin graft rejection in (P1 X P2)F1----P1 chimeras suggested that residual anti-P2 immunological capability in lethally irradiated P1 recipients may be associated with low P2 H-2 expression on their F1-derived spleen cells, although the mechanism does not involve selection of stable, variant F1 stem cells. The mechanism(s) of other classes of variation in H-2 expression in (P1 X P2)F1----P1 chimeras were not investigated.