Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion.
The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.
Katsenelson
Nora
N
Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Rockville, MD 20852-1448, USA.
Kanswal
Sunita
S
Puig
Montserrat
M
Mostowski
Howard
H
Verthelyi
Daniela
D
Akkoyunlu
Mustafa
M
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology*; D053301:B-Cell Maturation Antigen / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology*
D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; C486361:Tnfrsf13b 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