Antibody responses to (T,G)-A--L and (H,G)-A--L or to the TNP conjugates of these polypeptides, are regulated in the mouse by Ir genes encoded in the I-A subregion of the mouse MHC. To study the mechanism by which Ir genes function, it is essential to identify the cell interactions that are regulated by these genes. In the present report, it was specifically determined whether Ir gene function is expressed differently in the activation of B cell subpopulations that participate in two different pathways of B cell activation for in vitro antibody responses to TNP-(T,G)-A--L and TNP- (H,G)-A--L. The results of these studies demonstrate that under conditions that activate the Lyb-5- b cell subpopulation via MHC-restricted TH cell-B cell and TH cell-APC interactions, Ir gene function regulates TH cell interactions with these B cells as well as with APC. In addition, under conditions that activate the Lyb-5+ B cell subpopulation via MHC-restricted TH cell-APC but not TH cell-B cell interaction, Ir gene function regulates only TH cell interactions with APC but not with B cells.
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