A genetically restricted allogeneic effect factor (AEF) derived from a mixed lymphocyte culture reaction between Ia-negative activated responder cells and irradiated T-cell-depleted stimulator cells was characterized. Restricted AEF is a B-cell-derived soluble helper factor which consists in part of Ia antigens controlled by the I-A subregion of the stimulator haplotype; additional control by the I-B, I-E, and I-C subregions, although unlikely, could not be excluded. This factor helps B cells of only its own haplotype or of haplotypes which carry an I-A and/or I-B subregion identity. Unprimed as well as hapten-primed Ia-positive B cells express a receptor for restricted AEF. The results indicate that the B-cell receptor for AEF is determined by the I-A subregion. Both restricted AEF and its receptor may therefore be products of the same I-region gene(s). The data are compatible with the hypothesis that the AEF Ia antigens serve as a second signal required for B-cell activation to IgG antibody production.

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