Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor

• Published in: PloS one Vol. 11; no. 8; p. e0161161
• Main Authors: Samitas, Konstantinos, Malmhäll, Carina, Rådinger, Madeleine, Ramos-Ramirez, Patricia, Lu, You, Deák, Tünde, Semitekolou, Maria, Gaga, Mina, Sjöstrand, Margareta, Lötvall, Jan, Bossios, Apostolos
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.08.2016; Public Library of Science (PLoS)
• Subjects: Allergens; Allergies; Alveoli; Analysis; Animals; Apoptosis; Apoptosis - immunology; Asthma; Asthma - immunology; Asthma - metabolism; Asthma - pathology; B cells; B-Cell Activating Factor - metabolism; Bax protein; Biology; Biology and Life Sciences; Biomedical research; BLyS protein; Bone marrow; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - metabolism; Bronchial Hyperreactivity - pathology; Bronchoalveolar Lavage Fluid - immunology; Bronchus; Care and treatment; Case-Control Studies; ccr10 expression; CD40 antigen; CD86 antigen; Cells (biology); Chemotaxis; Clinical Medicine; Colonies; CXCR4 protein; Cytokines; Cytometry; differentiation; eosinophil progenitors; Eosinophils; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Exposure; factor baff; Female; Flow Cytometry; Humans; Hypersensitivity; Immunoglobulins; Immunology; In vivo methods and tests; Inflammation; Interleukin 7; Internal medicine; Klinisk medicin; Laboratories; Leukocytes (eosinophilic); Lungs; Lymphocyte receptors; Lymphocytes B; Male; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Middle Aged; Nutrition; Osteoprogenitor cells; Pneumonia - immunology; Pneumonia - metabolism; Pneumonia - pathology; Precursor Cells, B-Lymphoid - immunology; Precursor Cells, B-Lymphoid - metabolism; Precursor Cells, B-Lymphoid - pathology; Precursors; proliferation; Receptors; Research and Analysis Methods; Respiratory tract; Respiratory tract diseases; Risk factors; Science & Technology - Other Topics; secreting cells; Signal Transduction; Stem cells; survival
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161161

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. 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. 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. Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.