B cell tolerance to a minor, but not to a major, antigenic surface of the self antigen, cytochrome c.
To study B cell tolerance to the mitochondrial protein cytochrome c (CYT), the B cell response to pigeon CYT (PCC) was examined in mice transgenic for PCC. PCC was coupled to OVA to provide T cell help, since PCC-specific T cells in PCC-transgenic mice are deleted in the thymus. The frequency of secondary B cells responding to the minor antigenic surface around residue 44 on PCC was decreased about 10-fold in native PCC-transgenic mice compared with that in control mice or in transgenic 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 recognizing the site around residue 44 on mouse CYT compared with the frequency of B cells recognizing the corresponding site on foreign CYT. There were no major decreases but apparently were compensatory increases in the 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 CYT in cell death is discussed. This may be the first example of the use of a transgenic system to study B cell tolerance to a homologous self Ag.
Jemmerson
R
R
Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA. ron@lenti.med.umn.edu
Minnerath
J M
JM
Hedrick
S M
SM
Oehen
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D010856:Columbidae; D003574:Cytochrome c Group / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014644:Genetic Variation / Q000276:immunology; D007106:Immune Sera / Q000096:biosynthesis / Q000097:blood; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003574:Cytochrome c Group; D018985:Epitopes, B-Lymphocyte; D007106:Immune Sera