Human BCGF-12kD functions as an autocrine growth factor in transformed B cells.
In case of lymphoid malignancies of B cell origin and Epstein-Barr Virus (EBV) transformed B cells, it is invariably found that these cells proliferate in the apparent absence of signals from T cells. Many of transformed B cells tested appear to be refractory to the proliferative effects of a number of defined cytokines including IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, TNF alpha, lymphotoxin and IFN gamma. We have recently reported on the molecular cloning of a T cell derived human B cell growth factor, BCGF-12kD. In this study, we show that recombinant BCGF-12kD induces proliferation in EBV negative undifferentiated lymphoma B cell line, MC116 and Burkitt's lymphoma B cell line, P3HR1. A mouse monoclonal antibody produced against a BCGF-12kD synthetic peptide neutralizes the BCGF activity present in the MC116 conditioned media as well as inhibits the in vitro growth of MC116. The PCR analysis of the BCGF-12kD gene transcription provides further evidence that MC116 cells express the BCGF-12kD gene, whereas this gene is silent in resting and anti-IgM activated normal human B cells. These data clearly suggest an immunoregulatory role of BCGF-12kD in transformed human B cells.
Kumar
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Department of Pathology, Roger Williams General Hospital, Brown University, Providence, RI 02908.
Vasquez
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Maizel
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Sharma
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015847:Interleukin-4