Isolation and characterization of a monoclonal rheumatoid factor specific for the hinge region of rat IgG2b

The isolation and characterization of an isotype-specific autoantibody-secreting hybridoma NET/2/3 from rats bearing the syngeneic tumour HSN is described. This rheumatoid factor of the IgM class recognizes an epitope within the hinge region of rat immunoglobulins of the IgG2b subclass which is destroyed by reduction of disulphide bonds. The specificity of NET/2/3, although not allotype-restricted, is highly isotype-restricted, as it does not bind to rat Ig other than IgG2b, nor does it react with the majority of mouse IgG, although some reactivity occurs with mouse IgG3. One remarkable feature of NET 2/3 is that it binds more strongly to F(ab')2 and Fab' fragments of rat IgG2b, obtained by digestion with pepsin, than to the whole molecule. This anti-isotype response is not peculiar to the HSN tumour model as NET/2/3-like antibodies have been found in the sera of rats immunized with various protein and cellular antigens. The possible biological role of this anti-isotype antibody is discussed.