Induced cytokines include IFN-, MCP1, IL-6, TNF, MIP1, Rantes, IL-8 (55,100,107,113115). Dengue computer virus contamination and during alloimmunization, highlighting thein vivosignificance of this phenomenon. This review aims to summarize the current knowledge about human IgG1 Fc core fucosylation and its regulation and functionin vivo, in the context of both therapeutic antibodies and the natural immune response. The parallels in these two areas are useful about the mechanisms andin vivoeffects of Fc core fucosylation, and may allow to further exploit the desired properties of this modification in different clinical contexts. Keywords:therapeutic antibodies, IgG, N-glycan, fucosylation, ADCC, NK cells, computer virus, humoral response == Introduction == IgGs are among the most abundant proteins in the circulation (700-1600 mg/dl in healthy adults), and specific IgGs are induced in response to contamination, endogenous or allogeneic challenges, or by vaccination. Different IgG subclasses are found Influenza A virus Nucleoprotein antibody in man, which are very comparable structurally but have distinct functions due to their differential binding to FcRs, complement components as well as other proteins. About 60% of plasma IgG is usually IgG1, 32% IgG2 and 4% each IgG3 and IgG4 in humans (1). IgGs are glycoproteins and their glycosylation pattern can change during time, due to age, diseases or environmental factors (2,3). Therapeutic monoclonal antibodies (mAbs) have emerged as an important therapeutic option in cancer since the approval in 1997 of the anti-CD20 antibody rituximab for the treatment of B-non Hodgkin’s lymphoma (B-NHL). Since then, antibodies directed against different antigens expressed by cancer, immune cells or infectious brokers have been developed to treat a variety of diseases. Indeed, so far, over 130 antibodies have been approved by the US and EU Drug Agencies, with 45% for oncological disorders, 27% for immune- or inflammation-related conditions and the rest for infectious or other diseases (4). Most unconjugated therapeutic mAbs are IgG1 or in some cases IgG4 or IgG2. This is because the human IgG1 Fc moiety interacts efficiently with activating FcRs (FcRI, IIA, IIC, IIIA and IIIB), expressed on the surface of immune cells (1,5). This conversation leads to antibody-dependent cellular cytotoxicity (ADCC) by NK cells (mostlyviaFcRIIIA, CD16A) (6,7), antibody dependent phagocytosis (ADCP) by macrophages (mostly through FcRI, CD64 and to some extent FcRIIA, CD32A) (812) and ADCC/ADCP by polymorphonuclear neutrophils (PMN)(mostlyviaFcRIIA, CD32A) (1315). IgG1 also interacts with FcRIIIB (CD16B), a GPI-linked molecules lacking CP-690550 (Tofacitinib citrate) activating domain name, highly expressed by PMN and involved in PMN mediated ADCC and ADCP, but whose role may be either activating or inhibiting, perhaps depending on stimulus (1316). Immune cell activationviaFcRs also induces the release of cytokines and chemokines that may cooperate in eliminating the target cells but also induce unwanted side-effects (17). Finally the Fc region of human IgG1 can bind to the first component of the complement cascade C1q and activate the classical pathway of complement which may lead to cell lysis and death through complement dependent cytotoxicity (CDC), as well as phagocytosis by macrophages and PMN through complement receptors on these cells (18). Therefore, many therapeutic antibodies against cancer cells or other targets are of the IgG1 isotype to allow activation of a panoply of immune-mediated mechanisms, many of which rely on FcRs. When the activation of CP-690550 (Tofacitinib citrate) the immune system is not desired, for example when a therapeutic antibody is required only to neutralize the antigen, such as a growth factor or checkpoint inhibitor, then the human IgG4 or IgG2 subclasses are often chosen, because they do not interact efficiently with FcRs or with C1q. The more recent human IgG4 formats include a mutation in Fc. CP-690550 (Tofacitinib citrate)