Marginal Zone Formation Requires ACKR3 Expression on B Cells

Summary: The marginal zone (MZ) contributes to the highly organized spleen microarchitecture. We show that expression of atypical chemokine receptor 3 (ACKR3) defines two equal-sized populations of mouse MZ B cells (MZBs). ACKR3 is required for development of a functional MZ and for positioning of M...

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Main Authors: Egle Radice, Rafet Ameti, Serena Melgrati, Mathilde Foglierini, Paola Antonello, Rolf A.K. Stahl, Sylvia Thelen, David Jarrossay, Marcus Thelen
Format: Article
Language:English
Published: Elsevier 2020-08-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720309323
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author Egle Radice
Rafet Ameti
Serena Melgrati
Mathilde Foglierini
Paola Antonello
Rolf A.K. Stahl
Sylvia Thelen
David Jarrossay
Marcus Thelen
author_facet Egle Radice
Rafet Ameti
Serena Melgrati
Mathilde Foglierini
Paola Antonello
Rolf A.K. Stahl
Sylvia Thelen
David Jarrossay
Marcus Thelen
author_sort Egle Radice
collection DOAJ
description Summary: The marginal zone (MZ) contributes to the highly organized spleen microarchitecture. We show that expression of atypical chemokine receptor 3 (ACKR3) defines two equal-sized populations of mouse MZ B cells (MZBs). ACKR3 is required for development of a functional MZ and for positioning of MZBs. Deletion of ACKR3 on B cells distorts the MZ, and MZBs fail to deliver antigens to follicles, reducing humoral responses. Reconstitution of MZ-deficient CD19ko mice shows that ACKR3− MZBs can differentiate into ACKR3+ MZBs, but not vice versa. The lack of a MZ is rescued by adoptive transfer of ACKR3-sufficient, and less by ACKR3-deficient, follicular B cells (FoBs); hence, ACKR3 expression is crucial for establishment of the MZ. The inability of CD19ko mice to respond to T-independent antigen is rescued when ACKR3-proficient, but not ACKR3-deficient, FoBs are transferred. Accordingly, ACKR3-deficient FoBs are able to reconstitute the MZ if the niche is pre-established by ACKR3-proficient MZBs.
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spelling doaj.art-47796642acac49dea27c5c2ec17fc3712022-12-21T19:18:05ZengElsevierCell Reports2211-12472020-08-01325107951Marginal Zone Formation Requires ACKR3 Expression on B CellsEgle Radice0Rafet Ameti1Serena Melgrati2Mathilde Foglierini3Paola Antonello4Rolf A.K. Stahl5Sylvia Thelen6David Jarrossay7Marcus Thelen8Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Graduate School of Cellular and Molecular Sciences, University of Bern, 3012 Bern, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Graduate School of Cellular and Molecular Sciences, University of Bern, 3012 Bern, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Graduate School of Cellular and Molecular Sciences, University of Bern, 3012 Bern, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Graduate School of Cellular and Molecular Sciences, University of Bern, 3012 Bern, SwitzerlandIII Medizinische Klinik, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, SwitzerlandUniversità della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Corresponding authorSummary: The marginal zone (MZ) contributes to the highly organized spleen microarchitecture. We show that expression of atypical chemokine receptor 3 (ACKR3) defines two equal-sized populations of mouse MZ B cells (MZBs). ACKR3 is required for development of a functional MZ and for positioning of MZBs. Deletion of ACKR3 on B cells distorts the MZ, and MZBs fail to deliver antigens to follicles, reducing humoral responses. Reconstitution of MZ-deficient CD19ko mice shows that ACKR3− MZBs can differentiate into ACKR3+ MZBs, but not vice versa. The lack of a MZ is rescued by adoptive transfer of ACKR3-sufficient, and less by ACKR3-deficient, follicular B cells (FoBs); hence, ACKR3 expression is crucial for establishment of the MZ. The inability of CD19ko mice to respond to T-independent antigen is rescued when ACKR3-proficient, but not ACKR3-deficient, FoBs are transferred. Accordingly, ACKR3-deficient FoBs are able to reconstitute the MZ if the niche is pre-established by ACKR3-proficient MZBs.http://www.sciencedirect.com/science/article/pii/S2211124720309323ACKR3CXCR4CXCR5chemokineatypical chemokine receptormarginal zone B cell
spellingShingle Egle Radice
Rafet Ameti
Serena Melgrati
Mathilde Foglierini
Paola Antonello
Rolf A.K. Stahl
Sylvia Thelen
David Jarrossay
Marcus Thelen
Marginal Zone Formation Requires ACKR3 Expression on B Cells
Cell Reports
ACKR3
CXCR4
CXCR5
chemokine
atypical chemokine receptor
marginal zone B cell
title Marginal Zone Formation Requires ACKR3 Expression on B Cells
title_full Marginal Zone Formation Requires ACKR3 Expression on B Cells
title_fullStr Marginal Zone Formation Requires ACKR3 Expression on B Cells
title_full_unstemmed Marginal Zone Formation Requires ACKR3 Expression on B Cells
title_short Marginal Zone Formation Requires ACKR3 Expression on B Cells
title_sort marginal zone formation requires ackr3 expression on b cells
topic ACKR3
CXCR4
CXCR5
chemokine
atypical chemokine receptor
marginal zone B cell
url http://www.sciencedirect.com/science/article/pii/S2211124720309323
work_keys_str_mv AT egleradice marginalzoneformationrequiresackr3expressiononbcells
AT rafetameti marginalzoneformationrequiresackr3expressiononbcells
AT serenamelgrati marginalzoneformationrequiresackr3expressiononbcells
AT mathildefoglierini marginalzoneformationrequiresackr3expressiononbcells
AT paolaantonello marginalzoneformationrequiresackr3expressiononbcells
AT rolfakstahl marginalzoneformationrequiresackr3expressiononbcells
AT sylviathelen marginalzoneformationrequiresackr3expressiononbcells
AT davidjarrossay marginalzoneformationrequiresackr3expressiononbcells
AT marcusthelen marginalzoneformationrequiresackr3expressiononbcells