Apoptosis of Burkitt's lymphoma cells induced by specific interaction of surface IgM with a self-antigen: implications for lymphomagenesis in acquired immunodeficiency syndrome.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Apoptosis of Burkitt's lymphoma cells induced by specific interaction of surface IgM with a self-antigen: implications for lymphomagenesis in acquired immunodeficiency syndrome.

Blood. 1996 Jul 15;88(2):599-608. Unique Identifier : AIDSLINE MED/96289509
Roncella S; Cutrona G; Favre A; Ulivi M; Fais F; Signorini A; Grossi CE; Chiorazzi N; Ferrarini M; Servizi di Immunologia Clinica e Patologia Clinica, Istituto; Nazionale per la Ricerca sul Cancro-IST, Genova, Italy.

Abstract: In a previous study, we described a cell line (BRG-P) derived from a woman with Burkitt's lymphoma (BL) and acquired immunodeficiency syndrome that shared the same characteristic cytogenetic abnormalities as the patient's malignant cells. This cell line contained subclones that displayed an isotype switch from IgM to IgA1 and an accumulation of point mutations in the Vh region genes. Because these two features suggested an antigen-driven process, we began a search for the antigen responsible for the stimulation of the malignant B cells. Specifically, we hypothesized that because the patient's tumor had presented as a lymphomatous infiltration of the breast, the malignant B cells were recruited to this site because of the reactivity of their surface lg with breast tissue. A hybridoma (BRG-H) was obtained by fusing BRG-M cells (an IgM producing subclone of the BRG-P cell) with an appropriate cellular partner. The monoclonal antibody (BRG MoAb) produced by this hybridoma reacted strongly with two of five breast cancer cell lines and stained normal and malignant ductal epithelial cells on breast tissue sections. The antigen recognized by the BRG MoAb consisted of a single, minimally glycosylated polypeptide chain of 45 kD (p45). The BRG MoAb failed to react with a panel of human cell lines from different tissues, except for one cell line from a uterine cervical carcinoma. No reactivity was detected for a panel of exogenous antigens from various pathogens, including human immunodeficiency virus and self-antigens frequently recognized by polyspecific antibodies. Experiments were performed to investigate the functional consequences of the interaction of surface IgM with its specific ligand. Coculture of BRG-M cells with p45+, but not with p45-, breast cells caused apoptosis of BRG-M cells. The specificity of the interaction was shown by the observation that apoptosis was prevented by pretreatment of BRG-M cells with a monovalent F(ab') fragment of rabbit IgG antibody to human mu chains. Moreover, only BRG-M cells, but not other BL cells, underwent apoptosis after exposure to p45+ breast cells. The interaction between the CD40 molecule expressed by BRG-M cells and its specific ligand (CD40L) prevented p45-induced cell apoptosis. Because this interaction mimics that occurring in vivo between T and B cells during immune responses, our data suggest that various events contributed to the emergence of the BL, in this particular patient, including antigenic stimulation possibly assisted by T-cell help.

Keywords: Adult Animal Antibodies, Monoclonal/IMMUNOLOGY Antigen-Antibody Reactions Antigens, Neoplasm/*IMMUNOLOGY Apoptosis/*PHYSIOLOGY Autoantigens/*IMMUNOLOGY Breast/IMMUNOLOGY Breast Neoplasms/IMMUNOLOGY/*PATHOLOGY Burkitt's Lymphoma/IMMUNOLOGY/*PATHOLOGY Carcinoma, Infiltrating Duct/PATHOLOGY Cell Transformation, Neoplastic/*IMMUNOLOGY Coculture Epithelium/IMMUNOLOGY Female Human Hybridomas/IMMUNOLOGY IgM/*IMMUNOLOGY Immunoglobulins, Surface/*IMMUNOLOGY Isoantigens/*IMMUNOLOGY Lung Neoplasms/IMMUNOLOGY/PATHOLOGY Lymphoma, AIDS-Related/ETIOLOGY/IMMUNOLOGY/*PATHOLOGY Membrane Glycoproteins/PHYSIOLOGY Models, Biological Neoplasm Proteins/*IMMUNOLOGY Rabbits Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured JOURNAL ARTICLE
961130
M96B1875

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