title: B-cell agonists up-regulate AID and APOBEC3G deaminases, which induce IgA and IgG class antibodies and anti-viral function.
abstract: B cells express two critical deaminases in the development of adaptive and innate immunity. Activation-induced cytidine deaminase (AID) functions in class switch recombination, somatic hypermutation and may result in affinity maturation of antibodies. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G; A3G) is an innate anti-retroviral factor that inhibits HIV replication. We have studied a number of B-cell agonists with the aim of identifying the most effective agents that will up-regulate both deaminases and thereby enhance adaptive and innate immunity. CD40 ligand (CD40L) with interleukin-4 or HLA-class II antibodies significantly up-regulated both AID and A3G in isolated human CD19(+)  B cells. The functions of these deaminases were demonstrated by enhancement of B-cell surface expression of IgA and IgG and inducing significantly higher IgA and IgG4 antibodies. An enhanced A3G function was then demonstrated by inhibition of HIV-1 replication in co-culture of CD4(+)  T cells with autologous B cells, treated with CD40L and CD4 or HLA antibodies, compared with unstimulated human B cells. The dual B-cell-induced deaminase functions may be critical in IgA and IgG antibodies inhibiting pre-entry and A3G that of post-entry HIV-1 transmission and suggests a novel strategy of immunization, especially relevant to mucosal infections.
authors: Mucosal Immunology Unit, King's College London, Guy's Hospital, London, UK.
authors: Thomas
authors: T
authors: Seidl
authors: Trevor
authors: T
authors: Whittall
authors: Kaboutar
authors: K
authors: Babaahmady
authors: Thomas
authors: T
authors: Lehner
mesh_terms: D000071480:APOBEC-3G Deaminase; D056704:Adaptive Immunity; D000998:Antiviral Agents / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D001483:Base Sequence; D023201:CD40 Ligand / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000998:Antiviral Agents; C508598:IL4 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012333:RNA, Messenger; D023201:CD40 Ligand; D015847:Interleukin-4; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase