V beta gene family usage in spontaneous lymphomas of AKR mice: evidence for defective clonal deletion.
T-cell receptor (TCR) beta-chain usage and expression of the CD3, CD4, and CD8 differentiation antigens were analyzed in 14 spontaneous AKR lymphomas. Lymphoma cells massively infiltrated and/or proliferated in the organs analyzed (thymus, spleen, and mesenteric lymph nodes), giving rise to a loss of organ structure. One lymphoma occurred only in the thymus, and failed to express CD3, CD4, and CD8. All other lymphomas expressed the CD3/TCR complex. With respect to CD4 and CD8 expression, the lymphomas were either double-negative (DN), double-positive (DP), or single-positive (SP). The frequency of DP (CD4+8+) lymphomas was low compared to the frequency of DP thymocytes in a normal AKR thymus. A substantial heterogeneity was seen in the intensity of CD4 and CD8 expression among various lymphomas, which was independent of the level of CD3 expression. Considering TCR V beta gene family usage, 2 out of 14 lymphomas expressed V beta 6. Normally, V beta 6+ thymocytes are deleted from the thymocyte pool at the immature DP stage of T-cell development in AKR mice. These data support the hypothesis that the lymphocytes in the immature DP stage of T-cell development are susceptible to the induction of AKR lymphomagenesis. The presence of V beta 6+ lymphoma cells indicates that the lymphomagenesis is accompanied by a defective clonal deletion of cells expressing a possible autoreactive TCR.
De Heer
C
C
Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
De Geus
B
B
Schuurman
H J
HJ
Van Loveren
H
H
Rozing
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001483:Base Sequence; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology / Q000648:ultrastructure; D008223:Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013154:Spleen / Q000473:pathology / Q000648:ultrastructure; D013950:Thymus Gland / Q000473:pathology / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell