Work

Phospholipase Cγ2 Contributes to Light-Chain Gene Activation and Receptor Editing

Year: 2007

Type: article

Abstract: 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.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.02273-06