Role of ζPKC in B-cell signaling and function

The atypical protein kinase C isoform, ζPKC, has been implicated in the control of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB pathways. Recent evidence from ζPKC knock-out mice demonstrates that this kinase is important for NF-κB transcriptional activity but not for ERK activation in embryonic fibroblasts. The lack of ζPKC produces in mice a number of alterations in the development of secondary lymphoid tissues that could be accounted for, at least in part, by defects in B-cell function. Here, we present evidence that the loss of ζPKC selectively impairs signaling through the B-cell receptor, resulting in inhibition of cell proliferation and survival, as well as defects in the activation of ERK and the transcription of NF-κB-dependent genes. Furthermore, ζPKC–/– mice are unable to mount an optimal T-cell-dependent immune response. Collectively, these results genetically establish a critical role for ζPKC in B-cell function in vitro and in vivo.