Marginal Zone Formation Requires ACKR3 Expression on B Cells
Copyright policy )Marginal Zone Formation Requires ACKR3 Expression on B Cells
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.
- University of Bern Switzerland
- Universita della Svizzera Italiana Switzerland
- SIB Swiss Institute of Bioinformatics Switzerland
- University of Lausanne Switzerland
- Swiss National Science Foundation Switzerland
ACKR3, CXCR4, Mice, Knockout, Receptors, CXCR, B-Lymphocytes, Integrases, QH301-705.5, chemokine, Antigens, CD19, Green Fluorescent Proteins, Adoptive Transfer, CXCR5, Mice, Inbred C57BL, Animals, marginal zone B cell, atypical chemokine receptor, Biology (General), Antigens, Spleen
ACKR3, CXCR4, Mice, Knockout, Receptors, CXCR, B-Lymphocytes, Integrases, QH301-705.5, chemokine, Antigens, CD19, Green Fluorescent Proteins, Adoptive Transfer, CXCR5, Mice, Inbred C57BL, Animals, marginal zone B cell, atypical chemokine receptor, Biology (General), Antigens, Spleen
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