Related Experiment Video
Updated: Aug 8, 2026
Murine Model of CD40-activation of B cells
Published on: March 6, 2010
Lymphotoxin-alpha/beta heterodimer is expressed on leukemic hairy cells and activated human B lymphocytes
M Y Mapara1, R C Bargou, C Beck
1Free University of Berlin, Universitätsklinikum Rudolf Virchow-Robert Rössle Klinik, Department of Internal Medicine (Medical Oncology and Tumor Immunology), Berlin-Buch, Germany.
Insights
Human B cells express lymphotoxin (LT)-alpha/beta cell-surface complex upon activation. This complex is constitutively expressed on certain neoplastic B cells, like hairy-cell leukemia, indicating an activated state.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Lymphotoxin (LT) alpha/beta cell-surface complex plays a role in immune responses.
- Understanding LT expression in normal and neoplastic B cells is crucial for immunological research.
Purpose of the Study:
- To investigate the expression patterns of the human lymphotoxin (LT) alpha/beta cell-surface complex in various human B-cell contexts.
- To characterize the molecular nature and regulation of LT expression in normal and malignant B lymphocytes.
Main Methods:
- Studied LT expression in human B-cell lines, normal B lymphocytes, and neoplastic B cells (HCL, BCLL).
- Utilized immunoprecipitation, enzymatic digestion (F/N-glycosidase, O-glycosidase), and mRNA expression analysis.
- Investigated LT expression in response to in vitro activation using Staphylococcus aureus Cowan I (SAC).
Main Results:
- The human hairy-cell leukemia (HCL)-derived cell line JOK-I showed constitutive cell-surface LT expression, associated with a 25-kDa (N- and O-linked glycosylation) and a 33-kDa (N-linked glycosylation) molecule.
- Normal B cells expressed LT-beta mRNA constitutively, with sequential expression of LT-beta mRNA, LT-alpha mRNA, cell-surface LT, and LT secretion upon in vitro activation.
- Neoplastic B cells from chronic lymphocytic leukemia (BCLL) could be induced to express surface LT upon activation, and constitutive LT-beta transcripts were detected in most cases.
- Human HCL cells exhibited constitutive cell expression of both LT-alpha and LT-beta.
Conclusions:
- Cell-surface LT-alpha is expressed in association with LT-beta on activated normal B cells.
- Constitutive cell-surface LT expression on certain neoplastic B cells, like HCL, signifies an activated cellular state.
- LT-beta and LT-alpha are sequentially expressed in human B cells, with LT-beta appearing first, followed by LT-alpha upon activation.
Abstract:
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.
