The immune response modifiers imiquimod and R-848 are potent activators of B lymphocytes.
Imiquimod and R-848 are members of a family of immune response modifiers that stimulate cytokine production in monocyte/macrophages and dendritic cell cultures. This study evaluated the effects of the imidazoquinolines, imiquimod and R-848, on B lymphocyte activation. Both agents induced proliferation of murine T-cell-depleted and highly purified splenic B cell preparations as well as purified human B cells. Resting and activated B cells responded to these agents, with activated cells responding more efficiently. B cells from the LPS-hyporesponsive C3H/HeJ mice and guanosine-hyporesponsive SJL mice proliferated in response to imiquimod and R-848, indicating a different mechanism of action than lipopolysaccharide and guanine nucleosides. B cells were also stimulated by imiquimod and R-848 to produce increased immunoglobulin levels. Increased expression of a number of B cell activation markers were seen following imiquimod or R-848 stimulation. Finally, R-848 was shown to act as a vaccine adjuvant enhancing OVA-specific IgG2a levels while suppressing total IgE. These results indicate that R-848 and imiquimod are potent activators of B lymphocytes and are capable of augmenting antigen-specific immunoglobulin production.
Department of Pharmacology, 3M Pharmaceuticals, 3M Center, St. Paul, Minnesota 55144, USA.
M A
MA
Tomai
L M
LM
Imbertson
T L
TL
Stanczak
L T
LT
Tygrett
T J
TJ
Waldschmidt
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D006151:Guanosine / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D000077271:Imiquimod; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D007093:Imidazoles; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D006151:Guanosine; D007073:Immunoglobulin E; D010047:Ovalbumin; D000077271:Imiquimod; C402365:resiquimod