THE ROLE OF H-2-LINKED GENES IN HELPER T-CELL FUNCTION. III. Expression of Immune Response Genes for Trinitrophenyl Conjugates of Poly-L(Tyr,Glu)-Poly-D,L-Ala--Poly-L-Lys in B Cells and Macrophages* BY PHILIPPA MARRACK$ AND JOHN W. KAPPLER

For some years there has been intense interest in the problem of cellular expression of immune response (Ir) 1 genes. Initial experiments suggested that T cells alone were responsible for Ir manifestations since, for example, mice which were low responders to poly-L-(Tyr,Glu)-poly-D,L-Ala--poly L-Lys [(TG)-A--L] could make antibodies to this antigen coupled to methylated bovine serum albumin (1) and guinea pigs nonresponsive to the dinitrophenyl (DNP) hapten coupled to poly-L Lys could make antibodies to DNP coupled to other carriers (2). The idea of T-cell expression of Ir genes was strengthened by later experiments which showed that T cells from high responder strains could divide in response to the appropriate antigen, whereas T cells from low responder strains could not (3-5). In an elegant experiment, Bechtol et al. (6) showed that low responder B cells could make antibody to (TG)-A--L in tetraparental low responder ~ high responder mice. This result again suggested that Ir genes were not expressed in B cells. The role of macrophages (M6s), however, was not studied in any of these experiments. More recently, however, Ir genes have been found to be associated with B cells and/or Mobs. In the guinea pig, F1, low responder x high responder T cells proliferated when cultured with high responder Mobs pulsed with antigen, but not with low responder Mobs (7, 8). Similarly, Katz et al. (9) have shown in the mouse that F~, high responder x low responder T cells would help antibody responses of B cells from high responder mice, but not low responder mice to DNP-poly L-Glu, L-Lys, L-Tyr. Our work has shown that the Ir g,~ne controlling cross-reaction between sheep erythrocytes (SRBC) and burro erythrocytes (BRBC) at the helper T-cell level is expressed at least by the B cell in vitro (10, 11). The work of several laboratories (12-18) has suggested that at least three types of low responder animals can exist. The first type, exemplified by the response of mice of the H-