RESTRICTION OF PRIMARY RESPONSES TO THE IgG CLASS AND DEPENDENCY OF IgM RESPONSES ON SECONDARY IMMUNIZATION FOR THE COPOLYMERS OF L-GLUTAMIC ACID, L-TYROSINE, AND L-ALANINE* BY CARL WALTENBAUGH,$ JACQUES THI~ZE,§ ANn

The specific antibody responses of mice to thymus-dependent polypeptide antigens are controlled by autosomal dominant immune response (Ir) genes which map in the I region of the H-2 complex (1). Primary responses in vivo or in vitro to the linear copolymers GAT ~ (L-glutamic acide°-L-alanine3°-L-tyrosine ~°) and GA (L-glutamic acidJ°-L-alanine 5°) are restricted to the IgG class in responder mice (2-4). Similarly, in nonresponder mice primary responses to these antigens complexed to methylated bovine serum albumin (MBSA) and to GT (L-glutamic acidJ°-L-tyrosine 5°) as GT-MBSA are also restricted to the IgG class (2, 4, 5). These results are in sharp contrast with the early primary IgM responses to many conventional antigens such as sheep red blood cells (SRBC) bacterial antigens and to other synthetic polypeptide antigens (6, 7). Primary immunization with the linear terpolyper of L-glutamic acid, L-lysine, and L-phenylalanine (GLO) stimulates production of antibodies of the IgM and IgG class in responder animals but no responses in mice lacking the appropriate a ÷ and fl+ GLO genes (8, 9), whereas the branched copolymers studied by McDevitt and Sela have been shown to stimulate IgM antibody responses in both responder and nonresponder animals and IgG antibodies, only in responder strains (10, 11). The prevalent immunological dogma that the synthesis of IgM antibodies always precedes the development of IgG-forming cells as the initial response to antigen should, therefore, be re-examined. In this study, we have investigated the conditions necessary for the synthesis of specific IgM antibodies against GAT in responder strains and against GAT-MBSA or GT-MBSA in nonresponder strains of mice. In contrast to many classical antigens referred to above, specific IgM antibody responses to these antigens require secondary immunization.