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Molecular and Cellular Biology, September 2007, p. 5957-5967, Vol. 27, No. 17
0270-7306/07/$08.00+0     doi:10.1128/MCB.02273-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Phospholipase C{gamma}2 Contributes to Light-Chain Gene Activation and Receptor Editing{triangledown}

Li Bai,1,2,3 Yuhong Chen,1 Yinghong He,1,2,4 Xuezhi Dai,1 Xueyan Lin,3 Renren Wen,1 and Demin Wang1,5*

Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin 53226,1 Dali University, Dali, Yunnan 671000, People's Republic of China,2 School of Preclinical Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People's Republic of China,3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China,4 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 532265

Received 5 December 2006/ Returned for modification 17 January 2007/ Accepted 24 May 2007

Phospholipase C{gamma}2 (PLC{gamma}2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLC{gamma}2-deficient mice had reduced immunoglobulin {lambda} (Ig{lambda}) light-chain usage throughout B-cell maturation stages, including transitional type 1 (T1), transitional type 2 (T2), and mature follicular B cells. The reduction of Ig{lambda} rearrangement by PLC{gamma}2 deficiency was not due to specifically increased apoptosis or decreased proliferation of mutant Ig{lambda}+ B cells, as lack of PLC{gamma}2 exerted a similar effect on apoptosis and proliferation of both Ig{lambda}+ and Ig{kappa}+ B cells. Moreover, PLC{gamma}2-deficient IgHEL transgenic B cells exhibited an impairment of antigen-induced receptor editing among both the endogenous {lambda} and {kappa} loci in vitro and in vivo. Importantly, PLC{gamma}2 deficiency impaired BCR-induced expression of IRF-4 and IRF-8, the two transcription factors critical for {lambda} and {kappa} light-chain rearrangements. Taken together, these data demonstrate that the PLC{gamma}2 signaling pathway plays a role in activation of light-chain loci and contributes to receptor editing.


* Corresponding author. Mailing address: Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226. Phone: (414) 937-3874. Fax: (414) 937-6284. E-mail: demin.wang{at}bcw.edu

{triangledown} Published ahead of print on 25 June 2007.


Molecular and Cellular Biology, September 2007, p. 5957-5967, Vol. 27, No. 17
0270-7306/07/$08.00+0     doi:10.1128/MCB.02273-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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