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Suppression of Antibody Responses in Allogeneic Mice by Products of Lymphoid Tissue

I. Allogeneic Suppressive Factor (ASF) from Spleens Repopulated with Thymus Cells¹

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

A cellfree extract prepared from the spleen cells of C3H mice is capable of suppressing antibody responses to SRBC when extract material is exposed to alloantigens. The observed immunosuppression was attributed to a soluble factor in the extract. This allogeneic suppressive factor (ASF) was detected in extracts prepared from the spleen cells of unirradiated mice as well as those of irradiated mice repopulated with thymocytes, provided that mice were previously immunized with SRBC. Donors of actively suppressive ASF preparations did not need to be previously exposed to alloantigens. Extracts from thymus and marrow cells of unirradiated mice and the spleen cells of irradiated mice repopulated with marrow cells (or no cells) did not contain ASF. C3H thymocytes stimulated with SRBC generated more ASF activity in spleens of C3BF1 hosts than in those of C3H hosts, indicating that alloantigenic stimulation enhances the production or activity of ASF.

Once produced, C3H ASF was able to suppress antibody responses in cell transfer experiments only if exposed to C3BF₁ alloantigens of either donor lymphoid cells or irradiated hosts. Once exposed to alloantigens, ASF appears to be capable of suppressing antibody responses of syngeneic C3H or semi-allogeneic C3BF₁ cells. When both donor lymphoid cells and hosts were syngeneic with the donor of the ASF, there was enhancement of antibody formation in cell transfer experiments. C3H ASF did not interfere with education of C3BF₁ thymocytes to SRBC or with the generation of precusors of anti-SRBC antibody-forming cells by C3BF₁ marrow cells. ASF may interfere with cellular cooperative events necessary for humoral immune responses or with terminal differentiation of B cells. Production of ASF could partially account for the suppression of antibody responses observed during graft-vs-host reactions.

Footnotes

¹ Research supported in part by Grants RR 05648, CA 13377, CA 14801, and CA 15369 and Training Grant T01 CA0 5016 from the National Institutes of Health 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. 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, 80 East Concord Street, Boston, Massachusetts 02118.

³ M. B. is a recipient of Research Career Development Award CA 70879 from the National Institutes of Health.