title: BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis.
abstract: Prolonged infections or adjuvant usage can trigger emergency granulopoiesis (EG), leading to dysregulation in neutrophil blood counts. However, the impact of EG on T and B cell function remains largely unknown. In this study, to address this question, we used a mouse model of neutropenia and studied immune activation after adjuvant administration. The initial neutropenic state fostered an environment of increased dendritic cell activation and T cell-derived IL-17 production. Interestingly, neutropenic lysozyme 2-diphtheria toxin A mice exhibited striking EG and amplified neutrophil recruitment to the lymph nodes (LNs) that was dependent on IL-17-induced prostaglandin activity. The recruited neutrophils secreted a B cell-activating factor that highly accelerated plasma cell generation and antigen-specific antibody production. Reduction of neutrophil functions via granulocyte colony-stimulating factor neutralization significantly diminished plasma cell formation, directly linking EG with the humoral immune response. We conclude that neutrophils are capable of directly regulating T cell-dependent B cell responses in the LN.
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: Roham
authors.identifier: 0000-0002-0864-6098
authors.initials: R
authors.lastname: Parsa
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: Harald
authors.initials: H
authors.lastname: Lund
authors.affiliation: B Cell Biology, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Georgoudaki
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Neuroimmunology, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: André
authors.identifier: 0000-0002-4561-2823
authors.initials: A
authors.lastname: Ortlieb Guerreiro-Cacais
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: David
authors.identifier: 0000-0002-2666-1419
authors.initials: D
authors.lastname: Grommisch
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: Andreas
authors.identifier: 0000-0001-6588-1687
authors.initials: A
authors.lastname: Warnecke
authors.affiliation: Institute of Experimental Immunology, University of Zurich, CH-8057 Zürich, Switzerland.
authors.forename: Andrew L
authors.identifier: 0000-0003-4692-4746
authors.initials: AL
authors.lastname: Croxford
authors.affiliation: Neuroimmunology, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden.
authors.forename: Maja
authors.initials: M
authors.lastname: Jagodic
authors.affiliation: Institute of Experimental Immunology, University of Zurich, CH-8057 Zürich, Switzerland.
authors.forename: Burkhard
authors.identifier: 0000-0002-1541-7867
authors.initials: B
authors.lastname: Becher
authors.affiliation: B Cell Biology, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Mikael C I
authors.identifier: 0000-0001-5582-614X
authors.initials: MC
authors.lastname: Karlsson
authors.affiliation: Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital at Solna, S-171 76 Stockholm, Sweden Robert.Harris@ki.se.
authors.forename: Robert A
authors.identifier: 0000-0003-4990-509X
authors.initials: RA
authors.lastname: Harris
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D056724:Immunity, Humoral / Q000502:physiology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000502:physiology*; D009503:Neutropenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D020381:Interleukin-17; C505720:Tnfsf13b protein, mouse