The marginal zone (MZ) of the spleen contains a specialized set of innate-like B cells that are in direct contact with the blood. This study, published in Cell Reports, shows 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). Effective reconstitution of MZ deficient CD19ko mice with either of the two MZB subsets shows that ACKR3 negative MZBs can differentiate into the more mature ACKR3 positive MZBs, but not vice-versa. The phenotype of CD19ko mice lacking a MZ is readily rescued by the adoptive transfer of ACKR3-sufficient, but not -deficient follicular B cells (FOBs), indicating that ACKR3 expression is essential for the establishment of the MZ developmental niche. Accordingly, the inability of CD19ko mice to respond to T-independent antigen is rescued only when ACKR3-proficient, but not ACKR3-deficient FoBs are transferred. Moreover, ACKR3-deficient FOBs are able to reconstitute the MZ if the niche is pre-established by ACKR3 positive proficient MZBs.
ACKR3 expression marks two distinct marginal zone B (MZBs) cell populations. ACKR3 negative MZBs can differentiate into more mature ACKR3 positive MZBs, but not vice-versa. ACKR3 is required to form a proper marginal zone and to establish the correct microarchitecture of mouse spleen, which is necessary for an effective early immune response to T-independent antigens.
This article made the cover of the Cell reports issue. The cover shows the marginal sinus (green) of a mouse spleen section lining the white pulp at B cell follicles (blue). Radice et al. adoptively transferred atypical chemokine receptor 3 expressing (yellow) or not expressing (red) B cells into recipients, which were devoid of the marginal zone. Atypical chemokine receptor 3 expression is required to reconstitute the marginal zone and to mount a humoral immune response. Confocal images were taken and processed by Serena Melgrati and Marcus Thelen.