792 Genetic Control of Antibody Synthesis Results

Random-bred Swiss mice were bred selectively for their agglutinin responses to sheep and pigeon erythrocytes to obtain high and low responder lines for those antigens (1). After 20 generations, the two lines differed markedly in their mean agglutinin titers against sheep erythrocytes and were considered established, since the difference in agglutinin response could not be increased by further breeding (2). The two lines differed remarkably in their humoral responses not only against the antigens used for their selection but also against every antigen with which they have been tested: hen ovalbumin (3), Salmonella typhi (1), pneumococcal polysaccharide SIII (4), transplantation antigens (5), DNA hapten (6), and T4 bacteriophages (J. G. Howard, unpublished observations). Nevertheless, the high and low lines behaved alike in their cellular immune responses that are known to be expressions of thymus-derived cell function, such as contact reactivity (C. Stiffel, unpublished observations), graft-vs.host reaction, 1 allograft rejection (2), and phytohemagglutinin responsiveness (7). These findings suggested that the selection had operated primarily at the level of the bone marrow-derived cell, on genes concerned with differentiation for antibody synthesis regardless of immunological specificity (1). We confirmed this interpretation in an earlier study (8). The serum levels of individual immunoglobulins were measured in the two lines before and after antigenic challenge, and the immunoglobulin allotypes were determined. The levels of all immunoglobulins were shown to be depressed in the low line compared with the high line both before and after immunization with pigeon or sheep erythrocytes. The differences in immunoglobulin levels were more marked for IgM and IgG classes and subclasses than for IgA, and were considerably greater after immunization than before. The differences in immunoglobulin concentrations were considered to result from a deficiency in the low line, since in the high line the serum concentrations of