CXCR4(+) Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in the bone marrow Journal Article
| Authors: | Elias, S.; Sharma, R.; Schizas, M.; Valdez, I.; Rampersaud, S.; Park, S. M.; Gonzalez-Figueroa, P.; Li, Q. Z.; Hoyos, B.; Rudensky, A. Y. |
| Article Title: | CXCR4(+) Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in the bone marrow |
| 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. Inducible CXCR4 ablation in Treg cells results in dysregulation of B-1 B cells in the bone marrow due to local Treg cell depletion, leading to an increase in IgM autoantibody production and total IgM levels. |
| Keywords: | phenotype; differentiation; expression; mechanism; regulatory t-cells; chemokine receptor cxcr4; immune privilege; maintain |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 219 |
| Issue: | 7 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2022-07-04 |
| Start Page: | e20220047 |
| Language: | English |
| ACCESSION: | WOS:000861391900001 |
| DOI: | 10.1084/jem.20220047 |
| PROVIDER: | wos |
| PMCID: | PMC9178519 |
| PUBMED: | 35670812 |
| Notes: | MSK affiliated author Beatrice Hoyo's ORCiD profile does not reflect their full name -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work