Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides.
Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In mice, type A(D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to stimulate B cells. On the contrary, type B(K) CpG-ODNs are excellent B cell activators. Type C CpG-ODNs combine features of both types A(D) and B(K) CpG-ODNs. Despite cell type preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we show that a subset of B cells from lupus mice responds to type A(D) CpG-ODN stimulation vigorously and directly with increased CD25 and CD86 expression and IL-10 secretion. Furthermore, these CpG-ODNs induce high surface IgM expression and promote 50- to 100-fold higher IgM and IgG3 secretion in lupus B cells than in controls. This response is similar to that seen with bacterial DNA stimulation of B cells. Type A(D)-responsive cells are enriched within lupus B cells with the marginal zone (MZ) phenotype. These cells are at least twice more numerous in lupus mice than in controls. The ability of lupus B cells to respond to type A(D) CpG-ODN stimulation is not due to differential TLR9 expression. Therefore, type A(D) CpG-ODNs may contribute to the lupus pathogenesis by inducing MZ-B cell activation, costimulatory molecule expression, and polyclonal Ig secretion. Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages.
Brummel
Rachel
R
Division of Rheumatology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Lenert
Petar
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D006942:Hypergammaglobulinemia / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D009838:Oligodeoxyribonucleotides / Q000145:classification / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D015375:Receptors, Interleukin-2; D016753:Interleukin-10