Enhanced IgG 1 -mediated antibody response towards thymus-dependent immunization in CXCR1-deficient mice.

Autor: Jaufmann J; Department of Pharmacology, Experimental Therapy, and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany., Carevic M; Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tuebingen, Tuebingen, Germany., Tümen L; Department of Pharmacology, Experimental Therapy, and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany., Eliacik D; Department of Pharmacology, Experimental Therapy, and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany., Schmitt F; Department of Pharmacology, Experimental Therapy, and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany., Hartl D; Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tuebingen, Tuebingen, Germany.; Novartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland., Beer-Hammer S; Department of Pharmacology, Experimental Therapy, and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany.
Jazyk: angličtina
Zdroj: Immunity, inflammation and disease [Immun Inflamm Dis] 2021 Mar; Vol. 9 (1), pp. 210-222. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1002/iid3.380
Abstrakt: Background: Chemokine receptors and their corresponding ligands are key players of immunity by regulation of immune cell differentiation and migration. CXCR1 is a high-affinity receptor for CXCL8. Differential expression of CXCR1 is associated with a variety of human pathologies including cancer and inflammatory diseases. While various studies have highlighted the importance of CXCR1-mediated CXCL8-sensing for neutrophil trafficking and function, its role in B-cell responses remains unsolved. Therefore, our aim was to investigate innate and adaptive antibody responses in CXCR1-deficient mice.
Methods: Cell populations of the spleen and the peritoneal cavity were identified and quantified via flow cytometry. To investigate thymus-independent (TI) and thymus-dependent (TD) antibody responses, mice were immunized intraperitoneally with TNP-Ficoll, Pneumovax23, and TNP-Chicken Gamma Globulin. Mice were bled before as well as 7 and 14 days after vaccination to collect serum. Serum antibody levels overtime were analyzed according to their specificity by enzyme-linked immunosorbent assay. B-1 cell functionality was examined by IL-5/IL-5Rα-dependent stimulation of peritoneal and splenic cells in vitro. To analyze CXCR1/2-expression, CD19 + splenocytes were enriched by magnetic-activated cell sorting before isolation of total RNA contents, followed by reverse transcription and real-time polymerase chain reaction.
Results: The distribution of natural B-1 cell populations was disturbed in the absence of CXCR1, while their responsiveness towards TI antigens and in vitro stimulation remained functional. Besides, CXCR1-deficiency was accompanied by increased frequencies of follicular B-2 cells in the spleen. Interestingly, these mice produced elevated levels of antigen-specific IgG 1 upon TD immunization and harbored a significantly enlarged proportion of CXCR5-expressing T helper (H) cells. CXCR1-expression was detectable in CD19 + splenocytes derived from wild-type, but not CXCR1-deficient mice.
Conclusion: Our data demonstrate a previously unknown relevance of CXCR1 for the production of specific IgG 1 in response to vaccination. These findings identify CXCR1 as a promising candidate for future studies on the regulation of adaptive antibody responses.
(© 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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