CLONAL CHARACTER OF F1 HYBRID LYMPHOCYTE SUBSET RECOGNITION OF PARENTAL CELLS IN ONE-WAY MIXED LYMPHOCYTE CULTURES

Abstract

Proliferation of F1 hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F1 hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F1 hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F1 cells, and not the blocked parental cells, enter mitosis. Stimulation of F1 cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F1 recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F1 spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes.