Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Du, LK (Author) Other; Peng, RJ (Author) Other; Bjorkman, A (Author) Other; de Miranda, NF (Author) Other; Rosner, C (Author) Other; Kotnis, A (Author) Other; Berglund, M (Author) Other; Liu, CH (Author) Other; Rosenquist, R (Author) Other; Enblad, G (Author) Other; Sundstrom, C (Author) Other; Hojjat Farsangi, M (Author) Other; Rabbani, H (Author) Other; Manuel R Teixeira (Author) ICBAS; Revy, P (Author) Other; Durandy, A (Author) Other; Zeng, YX (Author) Other; Gennery, AR (Author) Other; de Villartay, JP (Author) Other; Pan Hammarstrom, Q (Author) Other

Journal

Title: Journal of Experimental Medicine

Vol. 209

Pages: 291-305

ISSN: 0022-1007

Publisher: Rockefeller University Press

Indexing

ISI Web of Knowledge - 29 Citations

Scopus - 36 Citations

Other information

Authenticus ID: P-002-D27

DOI: 10.1084/jem.20110325

Abstract (EN): Cernunnos is involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair. Here, we studied immunoglobulin (Ig) class switch recombination (CSR), a physiological process which relies on proper repair of the DSBs, in B cells from Cernunnos-deficient patients. The pattern of in vivo generated CSR junctions is altered in these cells, with unusually long microhomologies and a lack of direct end-joining. The CSR junctions from Cernunnos-deficient patients largely resemble those from patients lacking DNA ligase IV, Artemis, or ATM, suggesting that these factors are involved in the same end-joining pathway during CSR. By screening 269 mature B cell lymphoma biopsies, we also identified a somatic missense Cernunnos mutation in a diffuse large B cell lymphoma sample. This mutation has a dominant-negative effect on joining of a subset of DNA ends in an in vitro NHEJ assay. Translocations involving both Ig heavy chain loci and clonal-like, dynamic IgA switching activities were observed in this tumor. Collectively, our results suggest a link between defects in the Cernunnos-dependent NHEJ pathway and aberrant CSR or switch translocations during the development of B cell malignancies.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15