Kindlin‐3 maintains marginal zone B cells but confines follicular B cell activation and differentiation

Abstract: 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

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• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Journal of leukocyte biology. - 111, 4 (2022) , 745-758, ISSN: 1938-3673

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Härzschel, Andrea ; Li, Lixia ; Krenn, Peter W. ; Szenes‐Nagy, Eva ; Geoffroy, Andrieux ; Bayer, Elisabeth ; Pfeifer, Dietmar ; Polcik, Laura ; Denk, Ursula ; Höpner, Jan Philip ; Karabatak, Elif ; Danner, Danielle‐Justine ; Tangermann, Simone ; Kenner, Lukas ; Jumaa, Hassan ; Greil, Richard ; Börries, Melanie ; Ruppert, Raphael ; Maity, Palash C. ; Hartmann, Tanja

Weitere Informationen

• DOI: 10.1002/jlb.1hi0621-313r
• URN: urn:nbn:de:bsz:25-freidok-2231224
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.