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Biomedical subjects

M Wabl

Publications and source records attributed to M Wabl.

6 recordsLinked to original sources

A different sort of Mott cell.

NYC is a B lymphoma cell line derived from B/W mice. Upon fusion of NYC cells with a plasmacytoma, which itself produces no immunoglobulin, the resulting NYCH hybridoma cells are Mott cells; i.e., they contain large intracellular vesicles filled with immunoglobulin, the so-called Russell bodies. When NYCH.kappa, a variant of NYCH that had lost the ability to produce heavy chain, was transfected with a heavy-chain construct, this concentration of immunoglobulin in the intracellular vesicles occurred only when the transfected immunoglobulin heavy chain had the same variable region as NYC. Moreover, unlike conventional Mott cells, the hybrid cells secrete immunoglobulin at a normal rate.

Animals

Tumorigenesis mediated by an antigen receptor.

The heavy chain variable region of the immunoglobulin receptors on cells of the B lymphoma NYC are almost identical to that of other independent B-cell tumors of B/W mice. NYC IgM binds a viral antigen produced by the tumor cells; and despite extensive screening, immunoglobulin-negative variants were never found in the NYC cells, suggesting that NYC loses the capacity to grow in culture when it does not synthesize surface immunoglobulin. These findings indicate that the interaction of endogenous antigen with surface IgM continuously stimulates growth and, thus, that the tumorigenesis of B lymphomas in B/W mice is mediated by antigen receptors.

Animals

The murine IgG1/IgE class switch program.

Immunoglobulin class switching is controlled by cytokines. Thus, interleukin-4 (IL-4) directs class switching to both IgG1 and IgE. Consistent with this are the results reported here on restriction endonuclease analysis of active and inactive alleles of the IgH locus in IgE-producing cells. In cells that were stimulated in vitro by lipopolysaccharide and IL-4 the silent alleles preferentially switched to gamma 1, whereas in cells that were stimulated by antigen in vivo both active and inactive alleles switched to epsilon. Thirty percent of the recombined switch regions (S mu/S epsilon) contain S gamma 1 sequences, which we interpret as footprints of a previous switch to gamma 1. Since this percentage is a minimum estimate, between 30% and 100% of switching to epsilon must occur sequentially via gamma 1.

Animals

Bispecific antibodies that mediate killing of cells infected with human immunodeficiency virus of any strain.

Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gp120 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV-infected cells in vitro.

Acquired Immunodeficiency Syndrome

HeLa-LAV, an epithelial cell line stably infected with HIV-1.

An HeLa-LAV cell line was established by infecting and subcloning previously described CD4-expressing HeLa cells with HIV-1. Cells of this line stably synthesize all major HIV proteins, release infectious particles of HIV-1, but do not die even after long term culture. More than 90% of the cells express the envelope protein gp120 on the surface. The cells can be easily and efficiently labeled with 51chromium, and exhibit a low spontaneous release. Because they are susceptible to killing by allogeneic cytotoxic T cells (CTL) when targeted to gp120, they ought to be a useful source of target cells in any kind of HIV-specific killing assays. The cells may also help studies on HIV replication in non-lymphatic/non-monocytic cells. The HeLa-LAV cell line will be freely available from the AIDS Research and Reference Reagent Program.

CD4-Positive T-Lymphocytes