The effect of specific anti-I-J reagents on macrophage-T cell interactions was studied in an in vitro antibody response to burro erythrocytes. Macrophages were prepared from the spleens of F1 hybrid mice whose parental strains differed at the I-J subregion. Two F1 hybrids were used for these experiments, [B10.A(3R) X B10.A(5R)]F1 and [B10.S(9R) X B10.HTT]F1. F1 macrophages responded equally well with F1 T-B cells or with T-B cells of either parental strain. When F1 macrophages were pretreated with anti-I-J serum (without complement) specific for one parental haplotype, they were only able to cooperate with T helper (TH) cells of the unblocked haplotype and with F1 TH cells. Identical results were obtained with (Jb X Jk)F1 and (Js X Jk)F1 mice. The results indicate that TH cells possess genetically restricted receptors for macrophage I-J-subregion gene products and that the interaction between this receptor and the macrophage I-J-subregion determinants is essential for the initiation of a primary in vitro antibody response to an erythrocyte antigen.

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