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Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory
- Source :
- Immunity. 44:769-781
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Somatic hypermutation (SHM) and class-switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system.
- Subjects :
- 0301 basic medicine
Immunology
Somatic hypermutation
Mice, Transgenic
chemical and pharmacologic phenomena
Plasma cell
Article
Mice
03 medical and health sciences
0302 clinical medicine
Memory cell
Cytidine Deaminase
medicine
Activation-induced (cytidine) deaminase
Animals
Immunology and Allergy
B cell
Genetics
B-Lymphocytes
biology
Germinal center
Cell Differentiation
Cytidine deaminase
Germinal Center
Immunoglobulin Class Switching
Mice, Inbred C57BL
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Immunoglobulin class switching
Immunoglobulin G
biology.protein
Somatic Hypermutation, Immunoglobulin
Immunologic Memory
030215 immunology
Subjects
Details
- ISSN :
- 10747613
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....a9cb17f2503f782f79b98a64083726e3