Novel cross-reactive anti-idiotype antibodies with properties close to thehuman intravenous immunoglobulin (IVIg)

The most important link between the immune network theory and clinically us eful therapies so far is the use of human intravenous immunoglobulin (IVIg) in the treatment of autoimmune diseases, Although still controversial, one of the main mechanisms that has been postulated for the in vivo effects of IVIg, is the selection of immune repertoires through idiotypic interaction s, We describe here anti-idiotype IgG monoclonal antibodies (MAbs), which w ere obtained by immunization of syngeneic mice (Balb/c) with an anti-gangli oside antibody. These anti-idiotype MAbs show multiple idiotypic connection s and share some of the properties of the IVIg pool, The antiidiotype (Ab2) MAbs B7 and 34B7 showed heterogeneous binding with the idiotypes of severa l anti-ganglioside antibodies, MAbs obtained from splenocytes of nonimmuniz ed newborn mice, F(ab')(2) fragments of IgG human myeloma proteins, and non immunoglobulin antigens, The recognition pattern of the B7 MAb to the idiot ypes of human immunoglobulins was also studied using a phage display librar y obtained from the variable region genes of an asymptomatic AIDS patient a nd also F(ab')(2) fragments obtained from an IVIg pool of healthy human don ors, We also demonstrated that these MAbs produced some of the in vitro eff ects reported for the human IVIg pool, such as the inhibition of cell proli feration of human B and T cell lines and of normal human lymphocytes activa ted with different mitogens, Another striking property of the MAb B7 was it s ability to induce a dose-dependent specific antibody T-cell response in v ivo in syngeneic mice. Both anti-idiotype MAbs showed anti-metastatic effec t in vivo when injected intravenously to mice inoculated with MB16-F10 mela noma cells, The antimetastatic effect of the antiidiotype MAbs was not obse rved in athymic mice inoculated with the same tumor. This kind of antibody can become an interesting tool for further exploration of the role of idiot ypic network connections in the regulation of the immune system and to stud y the effects of interventions an network connectivity in experimental auto immune disease, using a reagent better chemically defined than the IVIg poo l.