Rectification of age-related impairment in Ig gene hypermutation during a memory response.
The deficiency in generating high-affinity antibodies due to impaired somatic hypermutation of Ig genes in the germinal center (GC) is considered the major mechanism responsible for the compromised humoral responses in aging. Since the intrinsic capability of aged B lymphocytes to respond to initial antigenic stimuli is largely intact and the expression of activation-induced cytidine deaminase, a key component required for Ig somatic hypermutation, is comparable between B cells from aged and young mice, it is possible to restore the age-related deficiency in the humoral response by circumventing the requirement for signals from other immune components. Here, we show that GC B cells from aged mice during a memory response carried mutated Ig genes with mutational frequencies comparable to that of GC B cells from young mice. Additionally, characterization of mutations in VDJ segments, and analysis of antibody-forming cells and antibodies demonstrated that the processes of antigen-driven clonal selection and affinity maturation are largely intact in aged animals. Thus, we conclude that the diminished antibody responses in aged animals may be significantly improved by repeated immunizations. These findings may have important implications in designing vaccines and immunization protocols for the elderly population and patients with certain immune deficiencies such as AIDS.
Han
Shuhua
S
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Marinova
Ekaterina
E
Zheng
Biao
B
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D003564:Cytidine Deaminase / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression / Q000502:physiology; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics / Q000276:immunology; D007125:Immunogenetics; D007074:Immunoglobulin G / Q000097:blood; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D014611:Vaccination; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D022801:Complementarity Determining Regions; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase