Marginal Zone Formation Requires ACKR3 Expression on B Cells
Egle Radice,
Rafet Ameti,
Serena Melgrati,
Mathilde Foglierini,
Paola Antonello,
Rolf A.K. Stahl,
Sylvia Thelen,
David Jarrossay,
Marcus Thelen
Affiliations
Egle Radice
Università 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, Switzerland
Rafet Ameti
Università 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, Switzerland
Serena Melgrati
Università 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, Switzerland
Mathilde Foglierini
Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
Paola Antonello
Università 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, Switzerland
Rolf A.K. Stahl
III Medizinische Klinik, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Sylvia Thelen
Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland
David Jarrossay
Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland
Marcus Thelen
Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Corresponding author
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.
