translation agency

IgM secreted by human T lymphoma virus-I-infected and transformed human B cell clones recognize a 66-kilodalton host-encoded protein.
Ng VL; Rainer C; Oliver MR; Marsh J; Wood P; Reyes GR; McGrath MS;
January 30, 1990
J Immunol. 1989 Oct 15;143(8):2501-7. Unique Identifier : AIDSLINE

It has previously been determined that transformed human B cells may be infected by and retain integrated human T cell lymphotropic virus, type I (HTLV-I). Although HTLV-I is primarily associated with transformation of human T lymphocytes, immortalized B cell populations have arisen after cocultivation of normal B cells and irradiated HTLV-I-infected T cells. To test whether HTLV-I infection might be involved in this B cell transformation process, we characterized five independent HTLV-I-infected and -immortalized human B cell clones. All five clones contained clonal HTLV-I integrations, expressed cell surface IgM, and secreted IgM in quantities varying from 0.1 to 4.0 micrograms/ml. Immunoblotting and immunoprecipitation of metabolically labeled cell lysates failed to detect synthesis of HTLV-I gag, env, or tat gene products, and cellular RNA dot blot analysis detected varying levels of HTLV-I gene transcripts in only three of the five clones. The secreted IgM from culture supernatants were affinity purified, and were found to selectively immunoprecipitate an acidic protein (isoelectric point = 5.0) of 66,000 m.w. (p66) from purified radioiodinated HTLV-I virions. This p66 copurified with metabolically labelled HTLV-I-infected B cell IgM from HKA-3 cells. Although HTLV-I RNA transcripts were present at low levels, the absence of HTLV-I proteins in HKA-3 cells made it unlikely that p66 was related to the major HTLV-I envelope glycoprotein, gp62. Anti-idiotypic mAb directed against the IgM produced by one B cell clone (HKA-3), as well as purified HTLV-I virions (containing p66), stimulated HKA-3 cell proliferation. Preincubating the anti-Id antibody or HTLV-I with excess HKA-3 IgM abolished the binding of either to HKA-3 cells. These data suggest that HTLV-I infected cells produce a cellular protein (p66), which is incorporated into and copurifies with HTLV-I virions, and which in at least one case (HKA-3) may act as a mitogenic stimulus, potentially contributing to the HTLV-I mediated transformation process.

Antibodies, Anti-Idiotypic/PHYSIOLOGY Antibodies, Monoclonal/PHYSIOLOGY B-Lymphocytes/IMMUNOLOGY/*METABOLISM/MICROBIOLOGY Blotting, Southern Cell Division Cell Line, Transformed Cell Transformation, Viral Clone Cells/IMMUNOLOGY/METABOLISM/MICROBIOLOGY Epitopes/ANALYSIS Human HTLV-I/*IMMUNOLOGY/METABOLISM/PHYSIOLOGY HTLV-I Infections/*METABOLISM IgM/*BIOSYNTHESIS/IMMUNOLOGY/PHYSIOLOGY Immunoglobulin Idiotypes/IMMUNOLOGY Molecular Weight Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Viral Proteins/*IMMUNOLOGY/METABOLISM Virion/PHYSIOLOGY JOURNAL ARTICLE