Regulatory B cells from hilar lymph nodes of tolerant mice in a murine model of allergic airway disease are CD5+, express TGF-β, and co-localize with CD4+Foxp3+ T cells.
In a biphasic, ovalbumin (OVA)-induced murine asthma model where allergic airway disease is followed by resolution and the development of local inhalational tolerance (LIT), transforming growth factor (TGF)-β-expressing CD5(+) B cells were selectively expanded locally in hilar lymph nodes (HLN) of LIT mice. LIT HLN CD5(+) B cells, but not LIT HLN CD5(-) B cells, induced expression of Foxp3 in CD4(+)CD25(-) T cells in vitro. These CD5(+) regulatory B cells (Breg) and CD4(+)Foxp3(+) T cells demonstrated similar increases in expression of chemokine receptors (CXCR4 and CXCR5) and co-localized in HLN B cell zones of LIT mice. The adoptive transfer of LIT HLN CD5(+) B cells, but not LIT HLN CD5(-) B cells, increased the number of CD4(+)Foxp3(+) T cells in the lung and inhibited airway eosinophilia in this OVA model. Thus, Breg in HLNs of LIT mice reside in a CD5(+) TGF-β-producing subpopulation and co-localize with CD4(+)Foxp3(+) T cells.
Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
P
P
Natarajan
A
A
Singh
J T
JT
McNamara
E R
ER
Secor
L A
LA
Guernsey
R S
RS
Thrall
C M
CM
Schramm
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D007108:Immune Tolerance; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D010047:Ovalbumin; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D015704:CD4 Antigens; D018956:CD5 Antigens; C514936:CXCR4 protein, mouse; C513179:CXCR5 protein, mouse; C526836:Cd5 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D016212:Transforming Growth Factor beta; D010047:Ovalbumin