Functional and genetic analysis of Ia antigens.

Using negative selection with anti-Ia serum and complement, Ia-"negative" lymphocyte populations give rise to clonal progeny which produce only IgM antibody, whereas Ia-positive lymphocytes generate B-cell progeny which produce IgG or both IgM and IgG antibody. The responder cell in the mixed lymphocyte reaction and the precursor and effector cells in cell-mediated lympholysis appear to be Ia-"negative" lymphocyte subpopulations. Helper T cells in some system are Ia-positive, and allotype suppressor T cells are also Ia-positive. Allogenic effect factor produced in the usual manner functions as an antigen nonspecific helper factor for several different H-2 haplotypes. However, when allogenic effect factor is produced from a mixed lymphocyte culture between responder lymphocytes treated with anti-Ia and complement and irradiated stimulator lymphocytes treated with anti-Thy-1.2 and complement, this "restricted" AEF is sharply restricted in the haplotypes it can stimulate. "Restricted" AEF produced in this manner with B10.BR responder cells and B10.S stimulator cells helps B10.S T-cell-depleted, hap-ten-primed spleen B cells but does not help B10.BR spleen cells. This raises the possibility that the Ia antigens in AEF may be derived from the stimulator B cells and/or macrophages rather than from the responder T cells.