B-CELL TOLERANCE TO A MINOR, BUT NOT TO A MAJOR, ANTIGENIC SURFACE OFTHE SELF ANTIGEN, CYTOCHROME-C

To study B cell tolerance to the mitochondrial protein cytochrome c (C YT), the B cell response to pigeon CYT (PCC) was examined in mice tran sgenic for PCC, PCC was coupled to OVA to provide T cell help, since P CC-specific T cells in PCC-transgenic mice are deleted in the thymus. The frequency of secondary B cells responding to the minor antigenic s urface around residue 44 on PCC was decreased about 10-fold in native PCC-transgenic mice compared with that in control mice or in transgeni c mice expressing an altered form of PCC that lacked the heme and had a different amino acid sequence at the N-terminus, A similar decrease has been observed in the frequency of B cells in normal mice recognizi ng the site around residue 44 on mouse CYT compared with the frequency of B cells recognizing the corresponding site on foreign CYT. There w ere no major decreases but apparently were compensatory increases in t he frequencies of B cells recognizing other sites on PCC in the native PCC-transgenic mice compared with those in other mice. These results indicate that B cells in mice are only partially tolerant to self CYT, A possible basis for this partial tolerance relating to the fate of C YT in cell death is discussed, This may be the first example of the us e of a transgenic system to study B cell tolerance to a homologous sel f Ag.