Monoclonal antibodies 14.18 (IgG3) and 11C64 (IgG3) directed against disialogangliosides GD2 and GD3, respectively, when used in conjunction with human peripheral blood mononuclear cells (PBMCs) stimulated with human recombinant interleukin (rIL-2) lyse both human melanoma and neuroblastoma cells by antibody-dependent cellular cytotoxicity. Such monoclonal antibody-"armed" effector cells are sp...

Enhancement of multiple effector functions of an antibody may be a promising approach for antibody therapy. We have previously reported that fucose removal from Fc-linked oligosaccharides greatly enhances antibody-dependent cellular cytotoxicity (ADCC) of therapeutic antibodies. Here, we report a unique approach to enhance complement-dependent cytotoxicity (CDC), another important effector func...

Evidence suggests that eosinophils contribute to inflammation in bronchial asthma by releasing chemical mediators and cytotoxic granule proteins. To investigate the mechanism of eosinophil degranulation in asthma, we established an in vitro model of allergen-induced degranulation. We treated tissue culture plates with short ragweed pollen (SRW) extract and sera from either normal donors or SRW-...

We observed and characterized paraproteins present in the serum of seven human immunodeficiency virus type 1 (HIV-1)-infected individuals. Immunoglobulin (Ig) subclass typing performed on these paraproteins identified five as IgG1 kappa, one as an IgG3 lambda, and one as an IgA lambda. The IgG1 kappa paraproteins, purified by high-pressure liquid chromatography, contained the majority of anti-H...

We have characterized a series of genetically engineered chimeric human IgG3 and IgG4 anti-dansyl (DNS) antibodies with identical antibody-combining sites but different hinge region amino acid compositions to determine how the hinge region influences Fab fragment segmental flexibility, C1q binding, and complement activation. Our data support the correlation between "upper hinge" length and Fab ...

The levels of subclass-specific immunoglobulin G (IgG) antibodies to five microbial antigens in normal human sera were measured by enzyme-linked immunosorbent assays (ELISA). The aim was to compare the IgG subclass profiles of specific antibodies to diverse antigens originating from virus, intra- and extracellular bacteria. Serum samples from 162 Danish women were analyzed for IgG1, IgG2, IgG3,...

CBA/N mice express an X-linked deficiency in their antibody response to many bacterial carbohydrates; we have shown recently that these antigens normally elicit antibody responses predominantly of the IgM and IgG3 isotypes. Here we demonstrate that mice, with the CBA/N phenotype have perferential deficiencies of IgM and IgG3 immunoglobulin expression, both when measured in serum and in cells se...

The route of transfer of anti-Borrelia duttonii antibody subclasses from mother to young and their role in protection against borrelial challenge infection in ddY mice were investigated. Offspring from infected and noninfected mice were segregated and nursed by noninfected or infected mothers. Enzyme-linked immunosorbent assay analysis of antibodies of the cross-suckled offspring revealed that ...

The protective efficacy of mAbs to Cryptococcus neoformans glucuronoxylomannan depends on Ab isotype. Previous studies in A/JCr and C57BL/6J mice showed relative protective efficacy of IgG1, IgG2a >> IgG3. However, we now report that in C57BL/6J x 129/Sv mice, IgG3 is protective while IgG1 is not protective, with neither isotype being protective in 129/Sv mice. IgG1, IgG2a, and IgG3 had differe...

Ab-based therapies have undergone a renaissance in recent years, but infusion-related reactions are a significant clinical problem. Administration of certain mAbs to Swiss Webster mice infected with Cryptococcus neoformans can result in acute lethal toxicity (ALT) characterized by cardiovascular collapse. The ability of a mAb to produce ALT is isotype dependent and occurs with IgG1 but not IgG3...