title: Non-CpG Oligonucleotides Exert Adjuvant Effects by Enhancing Cognate B Cell-T Cell Interactions, Leading to B Cell Activation, Differentiation, and Isotype Switching.
abstract: Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN) with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11.10 mice and the ovalbumin peptide recognized by the TCR as model antigen. We followed early activation events by measuring CD69 expression, late activation by MHC class II expression, cell division and antibody production of switched, and nonswitched isotypes. We found that both of the tested non-CpG ODN exerted significant immunomodulatory effects on early T cell and on late B cell activation events. Importantly, a synergism between non-CpG effects and T cell help acting on B cells was observed, resulting in enhanced IgG production following cognate T cell-B cell interactions. We propose that non-CpG ODN may perform as better adjuvants when a strong antigen-independent immune activation, elicited by CpG ODNs, is undesirable.
authors.affiliation: MTA-ELTE Immunology Research Group, 1/C Pázmány Péter Sétány, Budapest 1117, Hungary.
authors.forename: Melinda
authors.initials: M
authors.lastname: Herbáth
authors.affiliation: MTA-ELTE Immunology Research Group, 1/C Pázmány Péter Sétány, Budapest 1117, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Papp
authors.affiliation: MTA-ELTE Immunology Research Group, 1/C Pázmány Péter Sétány, Budapest 1117, Hungary ; Department of Immunology, Eötvös Loránd University, 1/C Pázmány Péter Sétány, Budapest 1117, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Erdei
authors.affiliation: MTA-ELTE Immunology Research Group, 1/C Pázmány Péter Sétány, Budapest 1117, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Prechl
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin