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Gene Review

Ly6d  -  lymphocyte antigen 6 complex, locus D

Mus musculus

Synonyms: Ly-61, Ly-6D, Ly61, Lymphocyte antigen 6D, ThB, ...
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Disease relevance of Ly6d

  • Although this profile suggested that MNU-induced lymphomas are phenotypically similar to a mature thymocyte subset, the presence of ThB antigen on Lyt-2+ L3T4- lymphomas did not support this notion [1].

High impact information on Ly6d

  • The Ly6d ligand (Ly6d-L) is a nonglycosylated protein of 9 kDa of broad distribution, rich in cysteine, with no discernable transmembrane sequence [2].
  • The majority of the lines corresponded phenotypically to Lyb-2+, Ly-5(B220)+, ThB- large pre-B cells, although some were classified as pro-B cells because of their Lyb-2+, Ly-17+, Ly-5(B220)- phenotype [3].
  • A small subpopulation of normal murine splenic B cells carrying all of the classic B cells markers (IgM, IgD, Ia, and ThB) also carries Ly-1, one of the major T cell surface molecules [4].
  • Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family [5].
  • The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia [5].

Biological context of Ly6d

  • Using these antibodies, we have studied a genetic polymorphism that is associated with the level of ThB expression on B lymphocytes but not with the antigen's expression on thymocytes [6].
  • The genetic map location near Ly-6 and the sequence similarity suggest that Thb and Ly-6 may have been derived from the same progenitor by gene duplication [7].
  • In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies [7].
  • In this study, using a gene expression screen, we show that Ly-6 (lymphocyte antigen 6 complex, locus D; mouse ThB), which belongs to a distinctive family of low molecular weight phosphatidyl inositol anchored cell surface glycoproteins, is upregulated in mouse liver with peroxisome proliferation [8].
  • The reason for the expression polymorphism is unknown and could include a different protein structure in ThB molecules, altered glycosylation, or differences in transcriptional control [9].

Anatomical context of Ly6d

  • While the latter four antigens were described as markers on mature T (or activated T and B) lymphocytes, ThB is restricted to immature thymocytes and all B cells [6].
  • We have generated three hybridomas producing rat monoclonal antibodies to a surface antigen, ThB, that is shared by murine B lymphocytes and approximately 50 percent of murine thymocytes [6].
  • Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related [5].
  • Spleen cells incubated with rat monoclonal antibodies to Lyt-1 (on all T cells) and ThB (on all B cells) were 95% removed by adherence to Petri dishes coated with antiserum to rat immunoglobulin [10].
  • ThB antigen is not detectable on migrant cells, but all subpopulations in the thymus are subdivided into two categories, bright and dull [11].

Associations of Ly6d with chemical compounds


Regulatory relationships of Ly6d

  • Monoclonal antibodies to ThB detect close linkage of Ly-6 and a gene regulating ThB expression [6].

Other interactions of Ly6d

  • ThB is not expressed on kidney, although some investigators (McKenzie et al. 1977 a, Halloran et al. 1978) report Ly-6 expression on that tissue [6].

Analytical, diagnostic and therapeutic context of Ly6d


  1. N-methyl-N-nitrosourea-induced and spontaneous AKR/J thymic lymphomas express distinct differentiation antigen phenotypes. Richie, E.R. Leuk. Res. (1988) [Pubmed]
  2. Ly6d-L, a cell surface ligand for mouse Ly6d. Apostolopoulos, J., McKenzie, I.F., Sandrin, M.S. Immunity (2000) [Pubmed]
  3. Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. Holmes, K.L., Pierce, J.H., Davidson, W.F., Morse, H.C. J. Exp. Med. (1986) [Pubmed]
  4. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. Hayakawa, K., Hardy, R.R., Parks, D.R., Herzenberg, L.A. J. Exp. Med. (1983) [Pubmed]
  5. The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion. Brakenhoff, R.H., Gerretsen, M., Knippels, E.M., van Dijk, M., van Essen, H., Weghuis, D.O., Sinke, R.J., Snow, G.B., van Dongen, G.A. J. Cell Biol. (1995) [Pubmed]
  6. Monoclonal antibodies to ThB detect close linkage of Ly-6 and a gene regulating ThB expression. Eckhardt, L.A., Herzenberg, L.A. Immunogenetics (1980) [Pubmed]
  7. Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB). Gumley, T.P., McKenzie, I.F., Kozak, C.A., Sandrin, M.S. J. Immunol. (1992) [Pubmed]
  8. Peroxisome proliferator-activated receptor alpha-dependent induction of cell surface antigen Ly-6D gene in the mouse liver. Dadras, S.S., Cook, W.S., Yeldandi, A.V., Cao, W.Q., Rao, M.S., Wang, Z., Reddy, J.K. Gene Expr. (2001) [Pubmed]
  9. Polymorphism at the mouse Thb locus. Gumley, T.P., McKenzie, I.F., Sandrin, M.S. Immunogenetics (1994) [Pubmed]
  10. Surface antigens on mouse natural killer cells: use of monoclonal antibodies to inhibit or to enrich cytotoxic activity. Seaman, W.E., Talal, N., Herzenberg, L.A., Herzenberg, L.A., Ledbetter, J.A. J. Immunol. (1981) [Pubmed]
  11. T cell maturation: thymocyte and thymus migrant subpopulations defined with monoclonal antibodies to the antigens Lyt-1, Lyt-2, and ThB1. Scollay, R., Weissman, I.L. J. Immunol. (1980) [Pubmed]
  12. A new murine model system for the in vitro development of thymoma cell heterogeneity. MacLeod, C.L., Hays, E.F., Hyman, R., Bourgeois, S. Cancer Res. (1984) [Pubmed]
  13. A gain of novel tissue specificity in the human Ly-6 gene E48. Brakenhoff, R.H., van Dijk, M., Rood-Knippels, E.M., Snow, G.B. J. Immunol. (1997) [Pubmed]
  14. Identification of a surface protein (p100) associated with two glycosyl-phosphatidylinositol-linked molecules (Thy-1 and ThB) by natural anti-lymphocyte autoantibodies. Lehuen, A., Monteiro, R.C., Kearney, J.F. Eur. J. Immunol. (1992) [Pubmed]
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