Heterogeneity of Phenotypic Expression in Normal and Neoplastic B-Cell Proliferations Detected by Monoclonal Antibodies LN-1 and DLC-48

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Abstract
Recently developed monoclonal antibodies DLC-48 and LN-1 have been shown to be effective reagents for complement-mediated cell lysis of human B-cells. The authors have initially found that these reagents are useful in elimination of malignant lymphomas cells from human bone marrow for autologous bone marrow transplantation. In the current study, the authors have further characterized the reactivity of these antibodies in B-cell neoplasia and have analyzed the heterogeneity of antigenic expression among benign and neoplastic lymphoid cells for B-cell monoclonal antibodies. With the use of quantitative flow cytometric techniques to assess heterogeneity of antigen expression, the findings indicate that phenotypic heterogeneity within neoplasms from individual patients exists for a number of B-cell-related monoclonal antibodies, including B1, common acute lymphocyte leukemia antigen (CALLA), Ia, Ba-1, DLC-48, and LN-1. Within a given histologic class of lymphoid neoplasia, phenotypic heterogeneity was found to be a property of some individual cases and not others for all B-cell monoclonal antibodies examined. This heterogeneity was not consistently expressed in patients with similar tumors, nor was it a consistent property of a given antigen. Using cell lines derived from large cell lymphomas, the authors were able to find phenotypic heterogeneity within neoplastic cell lines that can be used to develop models for dealing with phenotypic heterogeneity in the context of complement-mediated cell lysis. They also established that for DLC-48 and LN-1, the heterogeneity was not related to the phase of the cell cycle of the proliferating cells. The results suggest that single monoclonal antibody treatment for bone marrow depletion of neoplastic cell may be insufficient to overcome phenotypic heterogeneity of B-cell neoplasms.