title: Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor.
abstract: BACKGROUND
  B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive.
  
  
  METHODS
  A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls.
  
  
  RESULTS
  Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics.
  
  
  CONCLUSIONS
  Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Cellular Immunology Laboratory, Division of Cell Biology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.|7th Respiratory Medicine Dept. and Asthma Center, Athens Chest Hospital "Sotiria", Athens, Greece.
authors: Konstantinos
authors: http://orcid.org/0000-0002-9921-9859
authors: K
authors: Samitas
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Carina
authors: C
authors: Malmhäll
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Madeleine
authors: M
authors: Rådinger
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Patricia
authors: P
authors: Ramos-Ramirez
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: You
authors: Y
authors: Lu
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Tünde
authors: T
authors: Deák
authors: Cellular Immunology Laboratory, Division of Cell Biology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Maria
authors: M
authors: Semitekolou
authors: 7th Respiratory Medicine Dept. and Asthma Center, Athens Chest Hospital "Sotiria", Athens, Greece.
authors: Mina
authors: M
authors: Gaga
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Margareta
authors: M
authors: Sjöstrand
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Jan
authors: J
authors: Lötvall
authors: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Apostolos
authors: A
authors: Bossios
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053264:B-Cell Activating Factor / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D053264:B-Cell Activating Factor