Phospholipase Cgamma2 contributes to light-chain gene activation and receptor editing.
Phospholipase Cgamma2 (PLCgamma2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLCgamma2-deficient mice had reduced immunoglobulin lambda (Iglambda) 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 Iglambda rearrangement by PLCgamma2 deficiency was not due to specifically increased apoptosis or decreased proliferation of mutant Iglambda+ B cells, as lack of PLCgamma2 exerted a similar effect on apoptosis and proliferation of both Iglambda+ and Igkappa+ B cells. Moreover, PLCgamma2-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, PLCgamma2 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 PLCgamma2 signaling pathway plays a role in activation of light-chain loci and contributes to receptor editing.
Bai
Li
L
Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.
Chen
Yuhong
Y
He
Yinghong
Y
Dai
Xuezhi
X
Lin
Xueyan
X
Wen
Renren
R
Wang
Demin
D
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D054420:Pre-B Cell Receptors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
D007147:Immunoglobulin Light Chains; D050835:Interferon Regulatory Factors; D051966:Phospholipase C gamma; D054420:Pre-B Cell Receptors; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4