The immune response modifier resiquimod mimics CD40-induced B cell activation.
Members of the imidazoquinoline molecule family, including imiquimod and resiquimod (R-848), have potent antiviral and antitumor activities. Imiquimod cream (5%) (Aldara) is currently indicated for treatment of external genital and perianal warts. Previous characterization of these compounds has focused upon their ability to activate monocytes and dendritic cells, but recent studies have shown that resiquimod also stimulates B lymphocytes to proliferate and express an activated phenotype. This suggests that resiquimod could potentially serve as an effective vaccine adjuvant in stimulating a humoral immune response. This study shows that resiquimod mimics effects of the T-dependent CD40 signal in both mouse and human B cell lines. Resiquimod, like CD40, stimulates antibody secretion, cytokine production, protection from apoptosis, and CD80 upregulation. In addition, it shows synergy with signals delivered by the B cell antigen receptor and heightens CD40-mediated B cell activation, demonstrating that resiquimod can enhance antigen-specific responses in B lymphocytes.
Bishop
G A
GA
Department of Microbiology, VA Medical Center, Iowa City, Iowa 52242, USA. gail-bishop@uiowa.edu
Ramirez
L M
LM
Baccam
M
M
Busch
L K
LK
Pederson
L K
LK
Tomai
M A
MA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018899:CpG Islands / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007093:Imidazoles; D007075:Immunoglobulin M; D007155:Immunologic Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D014409:Tumor Necrosis Factor-alpha; C402365:resiquimod