ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/000/SRR8601880/SRR8601880.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/006/SRR8601876/SRR8601876.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/007/SRR8601877/SRR8601877.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/005/SRR8601875/SRR8601875.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/009/SRR8601879/SRR8601879.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/008/SRR8601878/SRR8601878.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/004/SRR8601874/SRR8601874.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR860/003/SRR8601873/SRR8601873.fastq.gzprimaryOK200GenomicsInstitute for Research in Biomedicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA523538Mus musculusThe marginal zone (MZ) of the spleen contains a specialized set of innate-like B cells that are in direct contact with the blood. Here we show that expression of the atypical chemokine receptor 3 (ACKR3) defines two phenotypically, transcriptionally and functionally distinct, equal-sized populations of mouse MZ B cells (MZBs). The ACKR3-expressing population is required for optimal development and function of the MZ and for the differentiation and positioning of all MZBs. In the absence of ACKR3 expression on B cells the MZ is distorted and the MZBs fail to deliver blood-borne antigens to follicular dendritic cells (FDCs), leading to a reduced early humoral immune response. Effective reconstitution of MZ deficient CD19ko mice with either of the two MZB subsets shows that ACKR3- MZBs can differentiate into the more mature ACKR3+ MZBs, but not vice versa. The phenotype of CD19ko mice lacking a MZ is readily rescued by the adoptive transfer of ACKR3-sufficient, and to a much lower degree by ACKR3-deficient follicular B cells (FoBs), indicating that ACKR3 expression is crucial for the establishment of the MZ developmental niche. Similarly, the inability of CD19ko mice to respond to T-independent antigen is rescued when ACKR3-proficient, but not ACKR3-deficient FoBs are adoptively transferred. Accordingly, ACKR3-deficient FoBs are able to reconstitute the MZ if the niche is pre-established by ACKR3 proficient MZBs. Our data uncover a new unexpected role of ACKR3 on B cells for forming the splenic microarchitecture. Overall design: RNA profile of ACKR3+ and ACKR3- mice MZBs were generated by deep sequencing with 4 mice/groupxref:PubMed:32755592ENAfalseTranscriptome analysis of ACKR3+ and ACKR3- Marginal Zone B cells (MZBs) in miceTranscriptome analysis of ACKR3+ and ACKR3- Marginal Zone B cells (MZBs) in mice2025-09-242020-06-22PRJNA523538GSE1268601009032755592