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.
Università della Svizzera Italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Cell Rep. 2020 Aug 4;32(5):107951. doi: 10.1016/j.celrep.2020.107951.
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 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 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.
边缘区 (MZ) 有助于高度组织化的脾脏微结构。我们表明，非典型趋化因子受体 3 (ACKR3) 的表达定义了两个相等大小的小鼠 MZ B 细胞 (MZBs) 群体。ACKR3 是功能性 MZ 发育和 MZBs 定位所必需的。B 细胞上 ACKR3 的缺失会扭曲 MZ，并且 MZBs 无法将抗原递送至滤泡，从而降低体液反应。MZ 缺陷型 CD19 小鼠的重建表明，ACKR3 MZBs 可以分化为 ACKR3 MZBs，但反之则不然。通过过继转移足够的 ACKR3 和较少的 ACKR3 缺陷滤泡 B 细胞 (FoBs) 可以挽救缺乏 MZ 的情况；因此，ACKR3 表达对于 MZ 的建立至关重要。当转移 ACKR3 功能正常但不是 ACKR3 缺陷的 FoBs 时，CD19 小鼠对 T 非依赖性抗原的反应能力得到挽救。因此，如果由 ACKR3 功能正常的 MZBs 预先建立了龛位，则 ACKR3 缺陷的 FoBs 能够重建 MZ。
