Most importantly, the inclusion of membrane-bound HSP70, secreted HSP70 or a combination significantly increased protection in mice challenged with EcoHIV,

a chimeric virus that replicates in mouse leukocytes in vivo. “
“B cells express two critical deaminases in the Pembrolizumab 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 CDK inhibitor 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. PAK5 Activation-induced cytidine deaminase (AID) and

apolipoprotein B mRNA-enzyme catalytic polypeptide-like 3G (APOBEC3G) are members of the APOBEC cytidine deaminase family of proteins.1,2 AID and APOBEC1 show significant homology and although APOBEC3G (A3G) appears to be a gene-duplication of AID protein3 there is limited homology between the two. AID is expressed in B cells inducing class switch recombination of the μ constant region to γ, α and ε, thereby changing the antibody isotype from IgM to IgG, IgA and IgE. AID is also essential in somatic hypermutation, introducing point mutations at the immunoglobulin gene variable region, which is responsible for affinity maturation and memory.4–6 Deamination is involved not only in antibody gene diversification by AID, but also in protection against retroviral DNA by A3G, mostly studied in CD4+ T cells, dendritic cells and macrophages as a mechanism against retroviral infections.1,7 Although A3G has been reported in B cells and higher levels were found in B cells than in monocytes,8 an anti-HIV-1 function of A3G in B cells, which lack the CD4 receptor for HIV-1, is unlikely. Although the anti-viral function of secretory IgA at mucosal surfaces is well recognized, the anti-viral function of A3G produced by B cells has not been studied.