Somatic hypermutation in T-independent and T-dependent immune responses to Haemophilus influenzae type b polysaccharide.
Secondary immune responses to T-independent antigens are characterized by little or no affinity maturation, a phenomenon attributed to limited somatic hypermutation. In the human immune response to Haemophilus influenzae type b capsular polysaccharide, however, there are numerous differences between rearranged heavy chain variable region gene segments and candidate germline genes, irrespective of antigen presentation in a T-independent or T-dependent form. To determine the characteristics of somatic hypermutation in this response, we analyzed rearranged heavy chain variable region segments and associated 3' untranslated JH4-JH5 introns from monoclonal anti-Hib PS antibodies. Mutation of untranslated introns and heavy chain variable segments in both T-independent and T-dependent responses resembles that described in murine and unselected human immune responses. Although mutation is frequent in both T-independent and T-dependent anti-Hib PS responses, there is little evidence of antigen-driven selection, suggesting that ongoing pressure to conserve the variable segment germline configuration limits affinity maturation in this immune response.
Adderson
E E
EE
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USA.
Shackelford
P G
PG
Carroll
W L
WL
D000907:Antibodies, Bacterial / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000235:genetics; D000955:Antigens, T-Independent; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D008969:Molecular Sequence Data; D009154:Mutation; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D011135:Polysaccharides, Bacterial; D004247:DNA