Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.
As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.
Cognasse
Fabrice
F
GIMAP-EA 3064, Université de Saint-Etienne, Faculté de Médecine, Saint-Etienne, France and EFS Auvergne-Loire, Saint-Etienne, France.
Acquart
Sophie
S
Beniguel
Lydie
L
Sabido
Odile
O
Chavarin
Patricia
P
Genin
Christian
C
Garraud
Olivier
O
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007136:Immunoglobulins; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D015703:Antigens, CD; C408982:CPG-oligonucleotide; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D023201:CD40 Ligand