Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation
العنوان: | Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation |
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المؤلفون: | Andrea Härzschel, Lixia Li, Peter W Krenn, Eva Szenes-Nagy, Geoffroy Andrieux, Elisabeth Bayer, Dietmar Pfeifer, Laura Polcik, Ursula Denk, Jan P Höpner, Elif Karabatak, Danielle-Justine Danner, Simone Tangermann, Lukas Kenner, Hassan Jumaa, Richard Greil, Melanie Börries, Raphael Ruppert, Palash C Maity, Tanja Nicole Hartmann |
المصدر: | Journal of Leukocyte Biology |
سنة النشر: | 2021 |
مصطلحات موضوعية: | B-Lymphocytes, Cytoskeletal Proteins, Mice, Phosphatidylinositol 3-Kinases, Integrin alpha4, Immunology, Cell Adhesion, Immunology and Allergy, Animals, Cell Biology, Lymphocyte Function-Associated Antigen-1 |
الوصف: | Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch. |
وصف الملف: | application/pdf |
اللغة: | English |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6eb32aeee778a60982ee5379aa0fd097 https://hdl.handle.net/21.11116/0000-000A-11B1-A21.11116/0000-000A-11AF-E21.11116/0000-000A-11B2-9 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....6eb32aeee778a60982ee5379aa0fd097 |
قاعدة البيانات: | OpenAIRE |
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