Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells.
Regulatory B cells control inflammation and autoimmunity in mice, including the recently identified IL-10-competent B10 cell subset that represents 1% to 3% of spleen B cells. In this study, a comparable IL-10-competent B10 cell subset was characterized in human blood. B10 cells were functionally identified by their ability to express cytoplasmic IL-10 after 5 hours of ex vivo stimulation, whereas progenitor B10 (B10pro) cells required 48 hours of in vitro stimulation before they acquired the ability to express IL-10. B10 and B10pro cells represented 0.6% and approximately 5% of blood B cells, respectively. Ex vivo B10 and B10pro cells were predominantly found within the CD24(hi)CD27(+) B-cell subpopulation that was able to negatively regulate monocyte cytokine production through IL-10-dependent pathways during in vitro functional assays. Blood B10 cells were present in 91 patients with rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, autoimmune vesiculobullous skin disease, or multiple sclerosis, and were expanded in some cases as occurs in mice with autoimmune disease. Mean B10 + B10pro-cell frequencies were also significantly higher in patients with autoimmune disease compared with healthy controls. The characterization of human B10 cells will facilitate their identification and the study of their regulatory activities during human disease.
Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Yohei
Y
Iwata
Takashi
T
Matsushita
Mayuka
M
Horikawa
David J
DJ
Dilillo
Koichi
K
Yanaba
Guglielmo M
GM
Venturi
Paul M
PM
Szabolcs
Steven H
SH
Bernstein
Cynthia M
CM
Magro
Armistead D
AD
Williams
Russell P
RP
Hall
E William
EW
St Clair
Thomas F
TF
Tedder
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
C508609:IL10 protein, human; C556062:IL10 protein, mouse; D016753:Interleukin-10