Frequency of clonal dominance in the specific antibody response to DNP-HSA in CBA and C57BL mice reflects their susceptibility to age-associated development of monoclonal gammopathies.

The effects of age, genetic background, and neonatal thymectomy on the levels and the heterogeneity of the specific antibody response were investigated in an experimental mouse model. Both intact and neonatally thymectomized (NTx) C57BL/KaLwRij (C57BL) and CBA/BrARij (CBA) mice were immunized at the age of 3 ("young") or 22 months ("old"). Highly sensitive antigen-specific immunoblotting techniques (ABL), in combination with agar-electrophoresis and isoelectric focusing (IEF), were used to investigate total specific antibody levels, the number of responding antigen-specific clonotypes, and the dominance of responding B cell clones in the antibody response against dinitrophenylated human serum albumin.

Development of aging-associated monoclonal gammapathies with antibody activity to the antigen used for immunization of young mice.

The influence of immunization with dinitrophenylated human serum albumin (DNP-HSA) at a young age on the development of age-related monoclonal gammapathies (MG) was investigated in a longitudinal study in intact and neonatally thymectomized (NTx) C57BL/KaLwRij and CBA/BrARij mice. Three-month-old mice were immunized four times in monthly intervals with DNP-HSA. Control mice received saline and adjuvant only.

Immunoblotting techniques for the detection of low level homogeneous immunoglobulin components in serum.

Because of the increasing demand for simple and reliable techniques for the detection of low concentrations of paraproteins against a highly heterogeneous serum background, two techniques were investigated for their sensitivity: isoelectric focusing (IEF) and Wieme high resolution electrophoresis, each with subsequent blotting by diffusion. The techniques were compared using isolated mouse monoclonal antibodies (mAb) of known concentration and specificity. Wieme electrophoresis in combination with immunoblotting (IBL) or antigen-specific immunoblotting (ABL) has a detection limit of 100 ng/ml and 10 ng/ml, respectively.

Side effects and immunogenicity of murine lymphocyte-specific monoclonal antibodies in subhuman primates.

The immediate side effects of lymphocyte-specific monoclonal antibody treatment of nearly 150 monkeys is documented in this study. Immediate side effects were only seen with antibodies specific for CD3 and CD8. These side effects are most likely related to stimulation of T cells to produce lymphokines (CD3) and/or to the rapid cell clearance (CD3 and CD8).

The internal image-like anti-idiotypic response to a CD3-specific monoclonal antibody in primates is dependent on the T cell-binding properties of the injected antibody.

Murine monoclonal antibodies used for therapeutic purposes generally elicit a strong antibody response. A large proportion of this response is specific for the idiotype of the injected monoclonal antibody. The CD3 T cell antigen is polymorphic in rhesus monkeys.

The effect of skin allograft survival of a monoclonal antibody specific for a polymorphic CD3-like cell surface molecule in rhesus monkeys.

FN18, a monoclonal antibody specific for the polymorphic rhesus monkey CD3 antigen on peripheral T cells, has been tested for its immunosuppressive effect in a rhesus monkey skin graft model. Animals were injected i.v.

Polymorphism for RhT3, a CD3-like cell surface antigen, expressed on rhesus monkey T lymphocytes.

The target antigen of the FN18 monoclonal antibody, called RhT3, is probably the rhesus monkey homologue of the human CD3 antigen, expressed on mature T cells. RhT3 appears to be polymorphic, since FN18 was not reactive with T cells from all the screened animals. Thus, immunofluorescent staining of peripheral blood lymphocytes with FN18 antibody revealed either a positive or a negative phenotype for the target antigen.

Differentiation antigens on rhesus monkey lymphocytes. II. Characterization of RhT3, a CD3-like antigen on T cells.

A monoclonal antibody FN18 is described, which is specific for mature rhesus monkey T lymphocytes. It defines a cell surface antigen, composed of two polypeptide chains with a molecular mass of 22 and 27 kDa. In view of these and other similarities with the human T3 or CD3 antigen, it was designated as RhT3.

Differentiation antigens on rhesus monkey lymphocytes. I. Identification of T cells bearing CD3 and CD8, and of a subset of CD8-bearing cells.

Rhesus monkeys provide an excellent preclinical model to test the effect of monoclonal antibodies (mAb) in vitro and in vivo. So far, mostly mAb have been used which were originally raised against human cell surface antigens but cross-reacted reasonably well with homologous antigens on rhesus monkey cells. However, to optimize the model, it was necessary to produce mAb which react specifically with subsets of rhesus monkey lymphocytes.

The influence of OKT8F treatment on allograft survival in rhesus monkeys.

The immunosuppressive effect of a monoclonal antibody specific for the cytotoxic/suppressor T cells (CD8) was investigated in rhesus monkeys. This antibody (OKT8F) removed the CD8-positive T cells from the circulation and prolonged skin allograft survival. Since most patients awaiting a kidney allograft are transfused prior to transplantation, the immunosuppressive potency of OKT8F was subsequently investigated in transfused recipients.