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B‐cell agonists up‐regulate AID and APOBEC3G deaminases, which induce IgA and IgG class antibodies and anti‐viral function
Author(s) -
Seidl Thomas,
Whittall Trevor,
Babaahmady Kaboutar,
Lehner Thomas
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03524.x
Subject(s) - cytidine deaminase , immunoglobulin class switching , somatic hypermutation , biology , antibody , b cell , apobec3g , activation induced (cytidine) deaminase , immunology , memory b cell , acquired immune system , virology , immune system
Summary 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.