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From the Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, New York 14203, and the Department of Pathology, Boston University School of Medicine, Boston, Massachusetts 02118
Abstract
Mice were irradiated, infused with thymocytes and immunized with a variety of antigens, i.e., sheep or horse red blood cells (SRBC or HRBC), diphtheria toxoid (DT) or bovine 
-globulin (BGG). The spleen cells (T.Spleen cells) were harvested 5 days later and cellfree extracts were prepared. The extracts contained an allogeneic suppressive factor (ASF) that was capable of inhibiting IgM antibody responses of allogeneic or semi-allogeneic unirradiated mice. ASF had to be injected within 24 hr of immunization to be effective and a single injection delayed, rather than abolished, the antibody response at the cellular level. However, daily injections of ASF resulted in persistent suppression of antibody response. ASF activity was antigen nonspecific, i.e., the antigen used to stimulate ASF production did not have to be the same as the antigen used to test for ASF activity. C3H T.Spleen extracts were even immunosuppressive when prepared by exposure to C3BF1 alloantigens only; such extracts suppressed antibody responses of C3BF1 and DBA/2 mice.
C3H ASF was removed from extracts after incubation with C3BF1 spleen cells but not after incubation with C3H spleen cells. C3BF1 spleen cells which had been preincubated with C3H ASF were unable to generate antibody-forming cells upon transfer to irradiated C3BF1 host mice. This suggests that the ASF molecule may be or include receptors for alloantigens.
The immunogenetic requirements for ASF activity were evaluated by injecting extracts from C3H, C57BL, C3BF1 and BALB/c T.Spleen cells into C3H, CBA, C57BL, BALB/c, DBA/2, A or C3H.A recipient mice. All extracts tested had ASF activity. However, all allogeneic recipients were not suppressed by the extract material. The suppressive activity of ASF seemed to require two (or more) antigenic differences between donors and recipients of extract material, an H-2K or I antigen difference and a second antigen difference, possibly Ig-1. In the limited numbers of strain combinations tested, T.Spleen extracts suppressed IgM antibody response only if exposed to H-2 and Ig-1 antigens, e.g., BALB/c (H-2d, Ig-1a) ASF suppressed A (H-2a, Ig-1e) but not C3H.A (H-2a, Ig-1a) or DBA/2 (H-2d, Ig-1c). Separate ASF molecules may react with separate antigens on the cell surface, i.e., with H-2 and G2a. Alternatively, one ASF molecule may react with two structurally associated antigens. If the latter is correct, it is conceivable that the 
2-microglobulin which is non-covalently linked to the major component of H-2 molecules expresses allotypic antigens coded for by Ig-1 and 2-microglobulin is one of the antigens recognized by ASF.
Footnotes
1 Research supported in part by Grants RR 05648, CA 13377, CA 14801, CA 15369, and Training Grant T01 CA 05016 from the National Institutes of Health, Grant IN-54 from the American Cancer Society, and Grant GB 35852 from the National Science Foundation.
2 In partial fulfillment of doctoral thesis requirements, State University of New York at Buffalo (Roswell Park Division), Buffalo, New York. D. Y. is a recipient of postdoctoral fellowship CA 02269 from the National Institutes of Health; present address, Department of Pathology, Boston University School of Medicine, Boston, Massachusetts 02118.
3 M. B. is a recipient of Research Career Development Award CA 70879 from the National Institutes of Health.
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