Dissect the function of PKCε in the formation of central supramolecular activation clusters and B cell activation (IRM8P.707)

Abstract Protein kinase C (PKC) is a family of kinases encoded by nine genes with redundant and meanwhile distinct biological functions. One of such member, PKCε, is abundantly expressed in B lymphocytes. However its roles in the formation of B cell immunological synapse (IS) and B cell activation are still unclear. Using a series of optical imaging based cell biological approaches, we showed that PKCε was efficiently recruited to the B cell IS after antigen and B cell receptor (BCR) engagement. The proper distribution of PKCε in IS is dependent on the bioactivity of PKCε as mutant PKCε in either constitutively activated or kinase dead format are unexpectedly extruded to peripheral region of IS. Over expression of WT PKCε but not its mutants enhanced the contraction of BCR toward the central supramolecular activation clusters (cSMACs) as determined by the contact area and the BCR fluorescence intensity and the percentage of cSMAC formation. We also found that the strength of the initiation of BCR signaling cascade was potently influenced by PKCε. The precise molecular mechanism of PKCε to enhance the cSMAC formation and B cell activation will also be discussed.