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The Immune Response of Mice Treated with Anti-µ Antibodies: The Effect on Antibody-Forming Cells, Their Precursors and Helper Cells Assayed in Vitro¹

From the Department of Immunology, Mayo Medical School, Mayo Clinic, Rochester, Minnesota 55901

Abstract

Previous studies have shown that mice treated from birth with heterologous anti-µ antiserum are severely immuno-suppressed with respect to numbers of splenic plaque-forming cells (PFC) to sheep red blood cells (SRBC) in all immunoglobulin classes. In this study we have investigated, using in vitro techniques, the cellular site of the deficit created by anti-µ. The primary PFC response of spleen cells originating from anti-µ-treated mice was completely suppressed in vitro. The response was restored by the addition to the cultures of B cells but not T cells. T cells were derived from normal spleens which had been depleted of B lymphocytes and adherent cells by filtration through cotton wool columns, or by educated thymus cells obtained from the spleens of lethally irradiated mice injected with syngeneic thymocytes and SRBC.

Restoration of the PFC response of spleen cells from anti-µ-treated mice by normal B cells suggested that a cellular deficiency rather than an activity process by inhibitory cells was the cause of the imunosuppression. Also, co-culturing spleen cells from normal and suppressed mice did not reveal the presence of inhibitory cells. Spleen cells from x-irradiated mice, injected with bone marrow from anti-µ-suppressed mice, gave rise to PFC cells when cultured with SRBC and normal T cells, suggesting that stem cells giving rise to B cells were not affected by anti-µ treatment. Similarly, educated thymus cells derived from suppressed mice could provide helper function when reconstituted in vitro with normal B cells. Exposure of normal bone marrow and spleen cells to anti-µ serum prior to passage through syngeneic x-irradiated recipients demonstrated that spleen cells were much more sensitive than were bone marrow cells to suppression by anti-µ antibodies. It is concluded that the target of anti-µ antibody is a µ-chain bearing B cell precursor to the IgM-, IgG-, and IgA-producing cell.

Footnotes

¹ Supported by grants from the Medical Research Council of Canada and Public Health Research Grant 5 RO 1 AM 17554.

² Research Associate of the Medical Research Council of Canada, Department of Surgery, Division of Surgical Research, Donner Building, McGill University, Montreal, Quebec, Canada.

³ Department of Immunology, Mayo Medical School, Rochester, Minnesota 55901.