Complement-fixing IgG1 constitutes a new subclass of mouse IgG

Abstract

Four IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) have been distinguished in the mouse^1–3. The similarity of the physico-chemical properties of the different isotypes has to a large extent prevented their purification from serum and this has complicated functional studies on IgG antibodies in sera from infected or immunised mice^1,2,4. The availability of immunoglobulin-secreting plasmacytomas⁵, however, has made the production of isotype-specific antisera possible; the use of these antisera has shown immunoglobulin of each isotype to exist in sera from normal animals^3,5,6. IgG1 antibodies, partially separated from IgG2 by electrophoresis in agar, have been reported² to be incapable of sensitising sheep red blood cells (SRBC), passively coated with antigen, for lysis by complement (C) although the antibodies agglutinated the cells and also mediated passive cutaneous anaphylactic (PCA) reactions in the mouse. The IgG2 antibodies, which mediated PCA reactions in the guinea pig but not in the mouse, lysed the antigen-coated SRBC in the presence of mouse C. It seems on the basis of this single report that mouse IgG1 has been widely accepted^6–8 to be a ‘non-C-fixing’ class of immunoglobulin—one which, on association with antigen, is unable to activate C. We have now purified IgG1 from the serum of mice immunised with SRBC and in this report present evidence that the IgG1 antibodies are not only haemolytic in the presence of C, but that they apparently account for more than half of the SRBC-specific, C-fixing IgG antibodies in the serum of the immunised animals.