Advanced live cell imaging studies suggested that B cell activation is initiated by the formation of BCR microclusters and subsequent B cell IS upon BCR and antigen recognition. PKC family member PKC beta is highly expressed in B cells and plays an important role in the initiation of B cell activation. Here, we reported an inhibitory function of PKC beta through a negative-feedback manner in B cell activation.

Compared with WT (PKC beta-WT) or the constitutively active (PKC beta-DNPS) form of PKC beta, DN PKC beta (PKC beta-DN) unexpectedly enhanced the accumulation of BCR microclusters into the B cell IS, leading to the recruitment of an excessive amount of pSyk, pPLC-gamma 2, and pBLNK signaling molecules into the membrane-proximal BCR signalosome.

Enhanced calcium mobilization responses in the decay phase were also observed in B cells expressing PKC beta-DN. Mechanistic studies showed that this negative-feedback function of PKC beta works through the induction of an inhibitory form of pBtk at S180 (pBtk-S180). Indeed, the capability of inducing the formation of an inhibitory pBtk-S180 is in the order of PKC beta-DNPS. PKC beta-WT. PKC beta-DN. Thus, these results improve our comprehensive understanding on the positive and negative function of PKC beta in the fine tune of B cell activation.