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Publication : Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.

First Author  Gitlin AD Year  2016
Journal  Immunity Volume  44
Issue  4 Pages  769-81
PubMed ID  26944202 Mgi Jnum  J:258602
Mgi Id  MGI:6142140 Doi  10.1016/j.immuni.2016.01.011
Citation  Gitlin AD, et al. (2016) Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory. Immunity 44(4):769-81
abstractText  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.
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