Phospholipase Cγ2 contributes to light-chain gene activation and receptor editing

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 Ig(HEL) 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.