Immune response gene (Ir-SRBC) exerts its effect via macrophages in inbred rats

In the previous report, strain differences of inbred rats were investigated in the antibody response to sheep erythrocytes (SRBC). A low-responder strain (Fischer rats) produced only IgM antibody, but other high-responder strains switched over from IgM to IgG antibody to SRBC. Pretreatment with incomplete Freund's adjuvant made Fischer rats a high-responder. These results seemed to indicate that there are malfunctions of macrophages, together with T cells, in Fischer rat strain. In this report, strain differences in the phagocytic activity of macrophages were examined using radiolabelled SRBC. High uptake of SRBC by the spleen in the low responder rats, and vice versa, was confirmed in various experimental conditions. Genetic analyses were made of the specific spleen uptake of the radiolabelled SRBC in backcrossed rats. The result clearly showed that the degree of spleen uptake of the radiolabelled SRBC is genetically determined by a single gene and this property itself has a close negative correlation with the ability of each rat to produce haemolysin against SRBC. These results strongly suggest that the Ir-SRBC gene exerts its effect, at least in part, via macrophages. The relationship between the function of the macrophage and the antibody response is discussed.