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.
Majumdar
A S
AS
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Guidos
C
C
Kaneshima
H
H
White
J H
JH
Marian
J
J
Lieberman
M
M
Weissman
I L
IL
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