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 CD19 ^ko 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 CD19 ^ko 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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)