The BALB/c Mouse B-Cell Response to Pigeon Cytochrome c Initiates as a Heteroclitic Response Specific for the Self Antigen Mouse Cytochrome c

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-12, Vol.92 (26), p.12379-12383
• Main Authors: Minnerath, J M, Wakem, L P, Comfort, L L, Sherman, F, Jemmerson, R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibody Formation; Antibody Specificity; Antigens; Autoantigens - immunology; B lymphocytes; B-Lymphocytes - immunology; Base Sequence; Binding Sites, Antibody; Chickens; Columbidae; Complementary DNA; Cytochrome c Group - biosynthesis; Cytochrome c Group - chemistry; Cytochrome c Group - immunology; Cytochromes; Immune response; Immunity (Disease); Mice; Mice, Inbred BALB C; Molecular Sequence Data; Mutagenesis, Site-Directed; Ova; Pigeons; Point Mutation; Rabbits; Rats; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Recombinant Proteins - immunology; Rodents; Saccharomyces cerevisiae; Sequence Homology, Amino Acid; Somatic mutation; Species Specificity; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.26.12379

Direct evidence is presented in support of the longstanding but unproven hypothesis that B lymphocytes specific for self antigens (Ags) can be used in the immune response to foreign Ags. We show that the B cells in BALB/c mice responding early to pigeon cytochrome c (CYT) produce antibodies that recognize and bind the major antigenic site on mouse CYT with greater affinity than they bind pigeon CYT- i.e., they are heteroclitic for the self Ag. Furthermore, these B cells express the same combination of immunoglobulin variable region (V) genes that are known to be used in B-cell recognition of mouse CYT. Over time, the response to pigeon CYT becomes more specific for the foreign Ag through the recruitment of B cells expressing different combinations of V genes and, possibly, somatic mutation of the mouse CYT-specific B cells from early in the response. Cross-recognition of pigeon CYT by mouse CYT-specific B cells results from the sharing of critical amino acid residues by the two Ags. Although B-cell recognition of the self Ag, mouse CYT, is very specific, which limits the extent to which foreign Ags can cross-activate the autoreactive B cells, it is possible that polyreactive B cells to other self Ags may be used more frequently in response to foreign Ags.