AID is required for germinal center-derived lymphomagenesis.

AID is required for germinal center-derived lymphomagenesis. Research Abstract Details 

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AID is required for germinal center-derived lymphomagenesis. Abstract Text:

Laura Pasqualucci,Govind Bhagat,Mila Jankovic,Mara Compagno,Paula Smith,Masamichi Muramatsu,Tasuku Honjo,Herbert C Morse,Michel C Nussenzweig,Riccardo Dalla-Favera,Laura Pasqualucci,Govind Bhagat,Mila Jankovic,Mara Compagno,Paula Smith,Masamichi Muramatsu,Tasuku Honjo,Herbert C Morse,Michel C Nussenzweig,Riccardo Dalla-Favera,Laura Pasqualucci,Govind Bhagat,Mila Jankovic,Mara Compagno,Paula Smith,Masamichi Muramatsu,Tasuku Honjo,Herbert C Morse,Michel C Nussenzweig,Riccardo Dalla-Favera,

Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR) before being selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant SHM, which arise from mistakes occurring during CSR and SHM. A direct link between these DNA remodeling events and GC lymphoma development, however, has not been demonstrated. Here we have crossed three mouse models of B cell lymphoma driven by oncogenes (Myc, Bcl6 and Myc/Bcl6; refs. 5,6) with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both CSR and SHM. We show that AID deficiency prevents Bcl6-dependent, GC-derived B-NHL, but has no impact on Myc-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of CSR- and SHM-mediated structural alterations. These results show that AID is required for GC-derived lymphomagenesis, supporting the notion that errors in AID-mediated antigen-receptor gene modification processes are principal contributors to the pathogenesis of human B-NHL.

AID is required for germinal center-derived lymphomagenesis. Publishing Authors By Initials

L Pasqualucci,G Bhagat,M Jankovic,M Compagno,P Smith,M Muramatsu,T Honjo,HC Morse,MC Nussenzweig,R Dalla-Favera,L Pasqualucci,G Bhagat,M Jankovic,M Compagno,P Smith,M Muramatsu,T Honjo,HC Morse,MC Nussenzweig,R Dalla-Favera,L Pasqualucci,G Bhagat,M Jankovic,M Compagno,P Smith,M Muramatsu,T Honjo,HC Morse,MC Nussenzweig,R Dalla-Favera,

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AID is required for germinal center-derived lymphomagenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature genetics

VOLUME: 40

Page Numbers: 108-12

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ISSN: 1546-1718

DAY: 9

MONTH: 12

YEAR: 2007

AID is required for germinal center-derived lymphomagenesis. Information

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LANGUAGE: eng

NlmUniqueID: 9216904

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AFFILIATION: Institute for Cancer Genetics, the Departments of Pathology and Genetics & Development, and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA. lp171@columbia.edu

Country: United States

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MEDLINETA: Nat Genet

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