An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets.
mAb 1C11 was raised against the cells of retrovirus-negative, radiation-induced thymomas of C57BL/Ka mice. MAb 1C11 binds to radiation- and RadLV-induced C57BL/Ka lymphomas, to lymphomas of other mouse strains and to B-lineage tumors. The 1C11 Ag is expressed on a subpopulation of normal thymocytes that is enriched in immature cells. After fractionated x-irradiation, this percentage increases gradually during the preleukemic period, hence mAb 1C11 appears to identify a transformation-related cell surface molecule. This conclusion is supported by experiments demonstrating that flow microfluorimetry-sorted, 1C11-expressing preleukemic thymocytes progress rapidly to full neoplasia following intrathymic injection, whereas nonexpressing cells do not. Most of day-14 fetal thymocytes are as strongly positive as thymic lymphomas for the 1C11 Ag whereas Ag-activated T cell lines express moderate levels. Multiparameter flow microfluorimetry analysis shows that 1C11 is expressed predominantly on CD3-/lo thymic blast cells of three phenotypically defined subsets: CD4-8-, CD4-8+, and CD4+8+, all of which contain thymic progenitors. By immunohistochemical staining, the Ag is also found in association with epithelial cells on a variety of normal, nonlymphoid tissue, but is not detectable on heart tissue. The 1C11 antibody immunoprecipitates a disulfide-linked heterodimeric protein of 85/37 kDa and the antigenic determinant is located on the H chain of the molecule. When analyzed by SDS-PAGE under nonreducing conditions, the molecule exists as a 130-kDa protein. Enzymatic digestion of the heterodimer indicates that the H chain, but not the L chain, has at least three N-linked glycosylation sites. We propose that this novel cell surface glycoprotein may be associated with processes of differentiation and lymphomagenesis.
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
A S
AS
Majumdar
C
C
Guidos
H
H
Kaneshima
J H
JH
White
J
J
Marian
M
M
Lieberman
I L
IL
Weissman
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D002454:Cell Differentiation; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D011289:Preleukemia / Q000276:immunology / Q000473:pathology; D013945:Thymoma / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008562:Membrane Glycoproteins