IFN type I and type II independent enhancement of B cell TLR7 expression by natural killer cells.
The PRR TLR7 plays a key role in the activation of autoantigen-reactive B cells. This response is increased markedly by IFN-α, produced by accessory cells, as a result of the up-regulation of TLR7. We report herein an alternative pathway by which TLR7 expression can be augmented. This finding was derived from continuation of ongoing studies to uncover interactions between NK and B cells. Here, we have compared gene expression profiles by microarray analysis of B cells before and after their interaction with purified NK cells. The most outstanding alteration of genes transcribed in B cells is a significant increase in the expression of many members of the ISG family, among which is TLR7. Further analysis revealed that the enhancement of TLR7 on B cells is not mediated via type I or type II IFN but by another cytokine, IL-28, a type III IFN, which acts in concert with contact-mediated interactions with NK cells. This increased expression allows B cells to respond more readily upon stimulation by its ligand and may increase in vivo responses to other TLR7 ligands, such as autoantigens, prior to or jointly with stimulation by other cytokines.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Suwan
S
Sinha
Yuhong
Y
Guo
Suwannee
S
Thet
Dorothy
D
Yuan
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D051940:B7-2 Antigen / Q000096:biosynthesis; D002450:Cell Communication; D016207:Cytokines / Q000502:physiology; D020869:Gene Expression Profiling; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D051199:Toll-Like Receptor 7 / Q000235:genetics*; D007378:Interleukins; D000095022:Interferon Lambda
D051940:B7-2 Antigen; D016207:Cytokines; D007370:Interferon Type I; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D051199:Toll-Like Receptor 7; C497965:Cd86 protein, mouse; C477038:Tlr7 protein, mouse; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda