Anti-self receptors. V. Properties of a mouse serum factor that blocks autorosetting receptors on lymphocytes.

Murine lymphocytes spontaneously bind autologous and allogeneic erythrocytes via receptors that primarily recognize self H-2L molecules on the erythrocyte surface. Normal mouse serum contains a factor, termed autorosette inhibition factor (AIF), that very effectively blocks autorosette formation. This paper describes experiments that determine the origin and nature of serum AIF. It was found that AIF lacks strain and species specificity, serum from several mammalian and non-mammalian species inhibiting the autorosetting of BALB/c thymocytes. However, mouse strains differed in the levels of AIF in their serum. Furthermore, AIF appears to directly interact with autorosetting receptors on lymphocytes as thymocytes from the BALB/c-H-2dm2 mutant strain, which lack autorosetting receptors, were unable to absorb the factor. Several lines of experimental evidence indicated that AIF is secreted by a population of short-lived, radiosensitive macrophages (or monocytes). Firstly, in vivo administration of the anti-macrophage agents carrageenan and silica profoundly depressed AIF levels in serum. Secondly, in vitro culturing of different lymphoid cells revealed that AIF is secreted by an adherent population of peritoneal cells. Thirdly, total body irradiation experiments demonstrated that AIF production is dependent upon a radiosensitive cell that is bone marrow derived. Finally, AIF was purified to homogeneity from mouse plasma and shown to be a single polypeptide chain with a molecular weight of 84,000.