Activation-induced cytidine deaminase mediates central tolerance in B cells.

Published

Journal Article

The Aicda gene product, activation-induced cytidine deaminase (AID), initiates somatic hypermutation, class-switch recombination, and gene conversion of Ig genes by the deamination of deoxycytidine, followed by error-prone mismatch- or base-excision DNA repair. These processes are crucial for the generation of genetically diverse, high affinity antibody and robust humoral immunity, but exact significant genetic damage and promote cell death. In mice, physiologically significant AID expression was thought to be restricted to antigen-activated, mature B cells in germinal centers. We now demonstrate that low levels of AID in bone marrow immature and transitional B cells suppress the development of autoreactivity. Aicda(-/-) mice exhibit significantly increased serum autoantibody and reduced capacity to purge autoreactive immature and transitional B cells. In vitro, AID deficient immature/transitional B cells are significantly more resistant to anti-IgM-induced apoptosis than their normal counterparts. Thus, early AID expression plays a fundamental and unanticipated role in purging self-reactive immature and transitional B cells during their maturation in the bone marrow.

Full Text

Duke Authors

Cited Authors

  • Kuraoka, M; Holl, TM; Liao, D; Womble, M; Cain, DW; Reynolds, AE; Kelsoe, G

Published Date

  • July 12, 2011

Published In

Volume / Issue

  • 108 / 28

Start / End Page

  • 11560 - 11565

PubMed ID

  • 21700885

Pubmed Central ID

  • 21700885

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1102571108

Language

  • eng

Conference Location

  • United States