Ig VH hypermutation is absent in the germinal centers of aged mice.
After injection with immunogenic conjugates of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP), two distinct B cell populations can be identified in the spleen during the primary response. One of these populations is specialized for Ab production; the other, the germinal centers (GCs), has been identified as the site of Ig somatic hypermutation. Ag-driven selection of GC B cells bearing mutated receptors with higher affinity leads to the affinity maturation of serum Ab and increased protective humoral immunity. Microdissection of GC B cell populations specific for NP and sequencing of the recovered Ig heavy chain variable region genes revealed that the somatic hypermutation process is absent in the GCs of aged C57BL/6 mice. However, selection for Ag appears to occur in the absence of hypermutation in the form of competition between unmutated clones of Ag-activated B lymphocytes. Thus, affinity maturation in these animals is limited to the affinities of Ab encoded by the germline.
Miller
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C
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201, USA.
Kelsoe
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G
D000367:Age Factors; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D005260:Female; D007109:Immunity; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D013154:Spleen / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid