title: A critical role for the protein kinase PKK in the maintenance of recirculating mature B cells and the development of B1 cells.
abstract: Protein kinase C associated kinase (PKK) regulates NF-κB 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 PKK 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-κB 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.
authors.affiliation: Division of Allergy/Immunology and Rheumatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States; Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States. Electronic address: luojing_chen@urmc.rochester.edu.
authors.forename: Luojing
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Allergy/Immunology and Rheumatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States; Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: David
authors.initials: D
authors.lastname: Oleksyn
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Pulvino
authors.affiliation: Division of Allergy/Immunology and Rheumatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sanz
authors.affiliation: Department of Pathology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ryan
authors.affiliation: Department of Pathology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ryan
authors.affiliation: Department of Pathology and Cell Biology & Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Chyuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Poligone
authors.affiliation: Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Alice P
authors.initials: AP
authors.lastname: Pentland
authors.affiliation: Division of Allergy/Immunology and Rheumatology, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ritchlin
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642, United States. Electronic address: jiyong_zhao@urmc.rochester.edu.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D017346:Protein Serine-Threonine Kinases; C430884:Ripk4 protein, mouse
keywords: B cells; B1 cells; PKK; Recirculating mature B cells