TLR-mediated stimulation of APC: Distinct cytokine responses of B cells and dendritic cells.
In addition to their role in humoral immunity, B lymphocytes are important antigen-presenting cells (APC). In the same way as other APC, B cells make cytokines upon activation and have the potential to modulate T cell responses. In this study, we investigated which mouse B cell subsets are the most potent cytokine producers, and examined the role of Toll-like receptors (TLR) in the control of secretion of IL-6, IL-10, IL-12 and IFN-gamma by B cells. Production of some cytokines was restricted to particular subsets. Marginal zone and B1 cells were the predominant source of B cell IL-10 in the spleen. Conversely, follicular B cells were found to express IFN-gamma mRNA directly ex vivo. The nature of the activating stimulus dramatically influenced the cytokine made by B cells. Thus, in response to combined TLR stimulation, or via phorbol esters, IFN-gamma was secreted. IL-10 was elicited by T-dependent activation or stimulation through TLR2, 4 or 9. This pattern of cytokine expression contrasts with that elicited from dendritic cells. QRT-PCR array data indicate that this may be due to differential expression of TLR signalling molecules, effectors and adaptors. Our data highlight the potentially unique nature of immune modulation when B cells act as APC.
Barr
Tom A
TA
Institute of Immunology and Infection Research, School of Biological Science, University of Edinburgh, Edinburgh, UK. tom.barr@ed.ac.uk
Brown
Sheila
S
Ryan
Gemma
G
Zhao
Jiexin
J
Gray
David
D
D000818:Animals; D016175:B-Lymphocyte Subsets; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D051193:Toll-Like Receptors