Genetic control of the in vitro responses of rat blood lymphocytes. II. Number of loci involved and linkage with in vivo antibody formation.

Blood lymphocytes from the inbred rat strains AS and BN differ in the magnitude both of their in vitro proliferative response to different mitogens and of their in vivo antibody response to the mitogenic fraction of phytohemagglutinin (PHA). We have examined the segregation of in vitro responsiveness to PHA in (AS X BN)F1 X BN backcross rats and have tried to correlate it with other characters that vary in backcross rats. In vitro responsiveness is regulated by one or a few loci, is linked to the in vitro responsiveness to B lymphocyte mitogens and the in vivo antibody response to the mitogenic fraction of PHA, but is not linked to the major histocompatibility locus (Ag-B) nor to the frequency of short-lived small Ig-negative lymphocytes in blood. Lymphocytes from high-responder rats have a shorter lag period before the onset of DNA synthesis in vitro than low-responder rats, and possibly also a higher number of in vitro responsing cells. To explain our findings, that the same gene og genes regulate in vitro responsiveness to different mitogens and in vivo antibody response to the mitogenic fraction of PHA, we suggest that the gene or genes act in an immunologically unspecific manner on the regulation of lymphocyte proliferation in vitro as well as in vivo.