|Title||Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Gitlin AD, von Boehmer L, Gazumyan A, Shulman, iv Z, Oliveira TY, Nussenzweig MC|
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.
|Grant List||R01 AI037526 / AI / NIAID NIH HHS / United States |
R01 AI072529 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.