CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in thebonemarrow

Shlomo Elias, Rahul Sharma, Michael Schizas, Izabella Valdez, Sham Rampersaud, Sun Mi Park, Paula Gonzalez-Figueroa, Quan Zhen Li, Beatrice Hoyos, Alexander Y. Rudensky*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    Regulatory T (Treg) cells represent a specialized lineage of suppressive CD4+ T cells whose functionality is critically dependent on their ability to migrate to and dwell in the proximity of cells they control. Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost the B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding the regulation of B cell autoreactivity and malignancies.

    Original languageEnglish
    Article numbere20220047
    JournalJournal of Experimental Medicine
    Volume219
    Issue number7
    DOIs
    Publication statusPublished - 2022

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