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Hodgkin's cell lectin, a lymphocyte adhesion molecule and mitogen
E Paietta1, R J Stockert, M McManus
1Department of Oncology, Montefiore Medical Center, Bronx, New York.
Insights
A novel Hodgkin's disease (HD) lectin on HD cells activates lymphocytes through both membrane-bound and secreted forms. This lectin, distinct from ICAM-1, may play a role in HD-associated immunodeficiency.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Hodgkin's disease (HD) cells express a novel galactose/N-acetylgalactosamine specific lectin activity (HD lectin) mediating lymphocyte adhesion.
- Both membrane-bound and secreted HD lectin activities are implicated in lymphocyte activation.
- Intercellular adhesion molecule-1 (ICAM-1) serves as an alternative binding site for peripheral blood lymphocytes (PBLs).
Purpose of the Study:
- To investigate the role of HD lectin and ICAM-1 in lymphocyte activation by HD cells.
- To identify the secreted factors from HD cells that contribute to lymphocyte activation.
- To explore the potential physiological relevance of HD lectin functions in HD-related immunodeficiency.
Main Methods:
- Utilized cultured HD cell lines (L428, L540) and their variants.
- Employed monoclonal antibodies (mAbs) against various cell surface molecules (CD2, CD3, CD4, CD8, CD11a, CD11b, CD11c) to block specific interactions.
- Analyzed lymphocyte activation, DNA synthesis, and conditioned media from HD cells.
Main Results:
- HD lectin, both membrane-bound and secreted, actively participates in activating agglutinated lymphocytes.
- ICAM-1 provides an alternative binding site for PBLs but is not essential for HD lectin-mediated stimulation.
- A soluble form of HD lectin, sharing properties with the membrane-bound form, was identified as a key factor in lymphocyte activation.
- HD cell membranes and conditioned media could stimulate resting lymphocytes, inducing DNA synthesis.
Conclusions:
- The HD lectin functions as both a lymphocyte adhesion molecule and a mitogen.
- Lymphocyte activation by HD cells is dependent on secreted factors, including the soluble HD lectin.
- The identified functions of HD lectin suggest a potential role in the severe immunodeficiencies observed in Hodgkin's disease patients.
Abstract:
We have previously shown a novel galactose/N-acetylgalactosamine specific lectin activity (Hodgkin's disease (HD) lectin) on the surface of cultured HD cells (lines L428, its variants, and line L540) to mediate lymphocyte adhesion. We here demonstrate that both surface membrane-bound and secreted HD lectin activities participate in the activation of agglutinated lymphocytes. Among known adhesion molecules expressed by the HD cells, only the intercellular adhesion molecule-1 (ICAM-1) contributed to this activation as an alternative PBL binding site. As yet we have not identified the cellular ligand(s) for the HD lectin on the lymphocyte surface. Pretreatment of lymphocytes with mAb to the accessory molecules CD2, CD3, CD4, CD8, CD11b, or CD11c did not interfere with their response to HD cells. mAb to CD11a (LFA-1), the alleged ligand of ICAM-1, inhibited the ICAM-1 but not the HD lectin-mediated lymphocyte stimulation. Although lymphocyte binding could proceed via either pathway, lymphocyte activation always depended upon factors secreted by the HD cells, one of which we identified as a soluble form of the HD lectin based on its shared properties with the membrane-bound form including immunologic cross-recognition and carbohydrate-binding specificity. Although HD cell-conditioned medium alone stimulated lymphocytes, HD cell plasma membranes could compensate for low concentrations of this medium. In addition, resting lymphocytes, normally unresponsive, were triggered into DNA synthesis by growth medium when cocultured with HD cell membranes. The unique functions of the surface-expressed HD lectin and its soluble counterpart as lymphocyte adhesion molecule and mitogen might be physiologically relevant to the severe immunodeficiencies occurring in patients with HD.