A critical role for the protein kinase PKK in the maintenance of recirculating mature B cells and the development of B1 cells

作者：Chen Luojing^*; Oleksyn David; Pulvino Mary; Sanz Ignacio; Ryan Daniel; Ryan Charlotte; Lin Chyuan sheng; Poligone Brian; Pentland Alice P; Ritchlin Christopher; Zhao Jiyong^*

来源：Immunology Letters, 2016, 172: 67-78.

DOI：10.1016/j.imlet.2016.02.015

• B cells
• PKK
• Recirculating mature B cells
• B1 cells

Protein kinase C associated kinase (PKK) regulates NF-kappa B activation and is required for the survival of certain lymphoma cells. Mice lacking PKK die soon after birth, and previous studies suggest that the role of PKK in B cell development might be context dependent. We have generated a mouse strain harboring conditional null alleles for PICK and a Cre-recombinase transgene under the control of the endogenous CD19 promoter. In the present study, we show that knockout of PKK in B cells results in the reduction of long-lived recirculating mature B cell population in lymph nodes and bone marrow as well as a decrease in peritoneal B1 cells, while PKK deficiency has no apparent effect on early B cell development in bone marrow or the development of follicular and marginal zone B cells in the spleen. In addition, we demonstrate that PKK-deficient B cells display defective proliferation and survival responses to stimulation of B cell receptor (BCR), which may underlie the reduction of recirculating mature B cells in PKK mutant mice. Consistently, BCR-mediated NF-kappa B activation, known to be required for the survival of activated but not resting B cells, is attenuated in PKK-deficient B cells. Thus, our results reveal a critical role of PKK in the maintenance of recirculating mature B cells as well as the development of B1 cells in mice.

• 出版日期2016-4