A negative-feedback function of PKC β in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse

J Leukoc Biol. 2015 May;97(5):887-900. doi: 10.1189/jlb.2A0714-320R. Epub 2015 Mar 4.


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 PKCβ 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 PKCβ through a negative-feedback manner in B cell activation. Compared with WT (PKCβ-WT) or the constitutively active (PKCβ-ΔNPS) form of PKCβ, DN PKCβ (PKCβ-DN) unexpectedly enhanced the accumulation of BCR microclusters into the B cell IS, leading to the recruitment of an excessive amount of pSyk, pPLC-γ2, 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 PKCβ-DN. Mechanistic studies showed that this negative-feedback function of PKCβ 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 PKCβ-ΔNPS > PKCβ-WT > PKCβ-DN. Thus, these results improve our comprehensive understanding on the positive and negative function of PKCβ in the fine tune of B cell activation.

Keywords: Btk; activation.