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Sökning: L773:0019 2805

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  • Shabani, Mahdi, et al. (författare)
  • Ligation of human Fc receptor like-2 (FCRL2) by monoclonal antibodies downregulates B cell receptor mediated signaling
  • 2014
  • Ingår i: Immunology. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 0019-2805 .- 1365-2567.
  • Tidskriftsartikel (refereegranskat)abstract
    • B cell antigen receptor (BCR) signaling and its regulation through negative and positive regulators are critical for balancing B cell response and function. Human Fc receptor like-2 (FCRL2), a member of the newly identified FCRL family, could influence B cell signaling due to possession of both immunoreceptor tyrosine-based activation and inhibitory motifs (ITAM and ITIM). Since the natural ligand of FCRL2 has not been identified yet, we generated FCRL2-specific monoclonal antibodies (mAbs) and employed them to investigate the influence of FCRL2 stimulation on BCR signaling in a FCRL2-expressing B cell line. Two anti-FCRL2 mAb-producing hybridoma clones (5A7-E7 and 3D8-G8) were selected. None of the mAbs displayed any cross-reactivity with the other members of the FCRL family including recombinant FCRL1, 3, 4 and 5, as tested by FACS and ELISA techniques. Engagement of the FCRL2 by these mAbs resulted in significant inhibition of BCR signaling mediators such as calcium mobilization and phosphorylation of the MAP kinases Erk, p38 and Jnk MAP. These findings indicate that the FCRL2 ITIM motifs are functional and the anti-FCRL2 mAbs may mimic the natural ligand of FCRL2 by induction of inhibitory signals in B cells.
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  • Albinsson, Sofie, et al. (författare)
  • Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation.
  • 2023
  • Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 169:1, s. 57-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+ CD8+ double-positive (DP) thymocytes and the CD4+ or CD8+ single-positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n=7) were compared regarding the expression of 34 molecules using cytometry by time-of-flight (CyTOF). In addition, FACS-sorted thymic eosinophils were co-cultured with autologous CD3/CD28-stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X-shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil-thymocyte co-cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.
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