TY - JOUR
T1 - CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in thebonemarrow
AU - Elias, Shlomo
AU - Sharma, Rahul
AU - Schizas, Michael
AU - Valdez, Izabella
AU - Rampersaud, Sham
AU - Park, Sun Mi
AU - Gonzalez-Figueroa, Paula
AU - Li, Quan Zhen
AU - Hoyos, Beatrice
AU - Rudensky, Alexander Y.
N1 - Publisher Copyright:
© 2022 Elias et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131772421&partnerID=8YFLogxK
U2 - 10.1084/jem.20220047
DO - 10.1084/jem.20220047
M3 - Article
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
M1 - e20220047
ER -