TLR stimulation modifies BLyS receptor expression in follicular and marginal zone B cells.
Through their differential interactions with B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), the three BLyS family receptors play central roles in B cell survival and differentiation. Recent evidence indicates BLyS receptor levels shift following BCR ligation, suggesting that activation cues can alter overall BLyS receptor profiles and thus ligand sensitivity. In this study, we show that TLR stimuli also alter BLyS receptor expression, but in contrast to BCR ligation, TLR9 and TLR4 signals, preferentially increase transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) expression. Although both of these TLRs act through MyD88-dependent mechanisms to increase TACI expression, they differ in terms of their downstream mediators and the B cell subset affected. Surprisingly, only TLR4 relies on c-Rel and p50 to augment TACI expression, whereas TLR9 does not. Furthermore, although all follicular and marginal zone B cells up-regulate TACI in response to TLR9 stimulation, only marginal zone B cells and a subset of follicular B cells respond to TLR4. Finally, we find that both BLyS and APRIL enhance viability among quiescent and BCR-stimulated B cells. However, although BLyS enhances viability among TLR stimulated B cells, APRIL does not, suggesting that TACI but not BLyS receptor 3 may share survival promoting pathways with TLRs.
Treml
Laura S
LS
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, PA 19104, USA.
Carlesso
Gianluca
G
Hoek
Kristen L
KL
Stadanlick
Jason E
JE
Kambayashi
Taku
T
Bram
Richard J
RJ
Cancro
Michael P
MP
Khan
Wasif N
WN
D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism; D015854:Up-Regulation
D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D020569:Proto-Oncogene Proteins c-rel; D018124:Receptors, Tumor Necrosis Factor; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; C491959:Tnfsf13 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13