4.8 Article

Marginal Zone Formation Requires ACKR3 Expression on B Cells

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CELL REPORTS
卷 32, 期 5, 页码 -

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CELL PRESS
DOI: 10.1016/j.celrep.2020.107951

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  1. Swiss National Science Foundation [310030_163336/1, CRSII3_160719]
  2. Helmut Horten Foundation
  3. Swiss National Science Foundation (SNF) [CRSII3_160719, 310030_163336] Funding Source: Swiss National Science Foundation (SNF)

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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.

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