Lymphotoxin-alpha/beta heterodimer is expressed on leukemic hairy cells and activated human B lymphocytes.
The expression of human lymphotoxin (LT) alpha/beta cell-surface complex was studied in human B-cell lines as well as in normal and neoplastic human B lymphocytes. In the absence of TNF receptors, only the human hairy-cell leukemia (HCL)-derived cell line JOK-I revealed constitutive cell-surface expression of LT but not TNF-alpha. Immunoprecipitation experiments with anti-LT monoclonal antibody (MAb) 9B9 from cell-surface radioiodinated JOK-I cells revealed that a cell-surface lymphotoxin molecule (25 kDa) is expressed in association with a 33-kDa molecule. Enzymatic digestion with F/N-glycosidase and O-glycosidase showed that both proteins contained N-linked carbohydrate residues, whereas only the 25-kDa molecule contained O-linked sugar residues. Analysis of mRNA expression revealed specific transcripts of LT-alpha and LT-beta in JOK-I cells. Resting tonsillar B cells did not express cell-surface LT. However, LT-beta mRNA was observable in unstimulated tonsillar B cells, whereas LT-alpha mRNA, cell-surface LT and LT secretion could only be detected upon in vitro activation. Thus LT-beta and alpha appear to be sequentially expressed in human B cells. Neoplastic B cells from chronic lymphocytic leukemia (BCLL), being devoid of constitutive cell-surface LT expression, could be induced to express surface LT by in vitro stimulation with Staphylococcus aureus Cowan I (SAC). Constitutive LT-beta transcripts, however, could also be detected in 4 out of 5 cases of BCLL. In contrast, human HCL cells displayed constitutive cell expression of lymphotoxin-alpha and beta. These findings demonstrate that cell-surface LT-alpha is expressed in association with LT-beta on activated normal B cells and neoplastic B cells representing an activated state.
Free University of Berlin, Universitätsklinikum Rudolf Virchow-Robert Rössle Klinik, Department of Internal Medicine (Medical Oncology and Tumor Immunology), Berlin-Buch, Germany.
M Y
MY
Mapara
R C
RC
Bargou
C
C
Beck
B
B
Heilig
B
B
Dörken
G
G
Moldenhauer
D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D006801:Humans; D015448:Leukemia, B-Cell / Q000473:pathology / Q000503:physiopathology; D007943:Leukemia, Hairy Cell / Q000503:physiopathology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000737:chemistry / Q000502:physiology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D008233:Lymphotoxin-alpha; D046911:Macromolecular Substances; D014409:Tumor Necrosis Factor-alpha