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Origin of Spleen Colonies Generated by Friend Virus-infected Cells in Mice¹

Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461

"Tumor colonies" develop in the spleen of unirradiated C57BL/6 x DBA/2 F₁ (hereafter called BD2F₁) mice (H-2^b/H-2^d) 9 days after i.v. injection of spleen cells from N-tropic Friend virus-infected DBA/2 donors (H-2^d/H-2^d). To determine whether these spleen colonies resulted from donor or host cell proliferation, we compared the histocompatibility antigen markers of cell populations from dissected colonies and intercolonial areas. Cytotoxic tests with mouse antisera specific for H-2D^b and H-2D^d antigens revealed the presence of both antigen specificities on cells from both sources, thus indicating that the majority of cells were of host BD2F₁ origin. The presence of donor cells in spleen colonies could be detected, however, when the recipients were lethally irradiated (800 R) BD2F₁ mice, the colonies of which consisted exclusively of cells bearing H-2D^d and not H-2D^b (recipient) antigens. Analogous results were obtained by cytotoxic analysis of spleen colonies in C57BL/6 x C3H/An F₁ mice injected with Friend virus-infected C3H/An spleen cells. In addition, direct visualization of virus-induced antigens and H-2 antigens by immunofluorescent staining confirmed the cytotoxicity data. Finally, the colony-forming efficiency of H-2^d cells was found to vary only slightly among unirradiated recipients of different H-2 haplotypes. These findings indicate that spleen colony formation by Friend virus-infected leukemia cells was based on donor cell proliferation in irradiated hosts and on host cell proliferation in unirradiated hosts, for the strains used here. The spleen colony assay for Friend leukemia cells in unirradiated hosts is therefore an assay for infectious centers where virus is apparently released from donor cells in quantities sufficient to infect Fv-1-restrictive host cells and to initiate their proliferation.

¹ This work was supported by Grant CA 14529 and USPHS Contract NO1 CP 71017 from the National Cancer Institute, Department of Health, Education, and Welfare. Part of this work was presented at the 68th Annual Meeting of the American Association for Cancer Research, Denver, Colo., May 18 to 21, 1977 (16).

² To whom requests for reprints should be addressed, at Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, N. Y. 10461.

³ Chargé de Recherches at Institut National de la Santé et de la Recherche Médicale, France. Recipient of a fellowship from the Cancer Research Institute, Inc.

Received 3/ 6/78. Accepted 5/30/78.

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