title: Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers.
abstract: Exceptionally germinal center formation can be induced without T cell help by polysaccharide-based antigens, but these germinal centers involute by massive B cell apoptosis at the time centrocyte selection starts. This study investigates whether B cells in germinal centers induced by the T cell-independent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation in their immunoglobulin V region genes. Positive controls are provided by comparing germinal centers at the same stage of development in carrier-primed mice immunized with a T cell-dependent antigen: NP protein conjugate. False positive results from background germinal centers and false negatives from non-B cells in germinal centers were avoided by transferring B cells with a transgenic B cell receptor into congenic controls not carrying the transgene. By 4 d after immunization, hypermutation was well advanced in the T cell-dependent germinal centers. By contrast, the mutation rate for T cell-independent germinal centers was low, but significantly higher than in NP-specific B cells from nonimmunized transgenic mice. Interestingly, a similar rate of mutation was seen in extrafollicular plasma cells at this stage. It is concluded that efficient activation of hypermutation depends on interaction with T cells, but some hypermutation may be induced without such signals, even outside germinal centers.
authors.affiliation: Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom.
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: William E
authors.initials: WE
authors.lastname: Jenkinson
authors.forename: Dale R
authors.initials: DR
authors.lastname: Taylor
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Daniel M-Y
authors.initials: DM
authors.lastname: Sze
authors.forename: David M
authors.initials: DM
authors.lastname: Sansom
authors.forename: Carola G
authors.initials: CG
authors.lastname: Vinuesa
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D020296:Animals, Congenic; D000955:Antigens, T-Independent / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007114:Immunization; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000955:Antigens, T-Independent; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D004247:DNA