Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects.

Background: Several recent reports have connected protein methylation with differentiation. Furthermore, the BTG/TOB proteins have also been implicated in such control. BTG1 and 2 have been shown to interact with PRMT1 (predominant cellular arginine N-methyltransferase of type I).

Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle.

It is well known that loss of tumor suppressor genes and more generally of antiproliferative genes plays a key role in the development of most tumors. We report here the cloning of the mouse BTG3 gene and show that its human counterpart maps on chromosome 21. This evolutionarily conserved gene codes for a 30 kDa protein and is expressed in most adult murine and human tissues analyzed.

Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway.

Cell cycle regulation is critical for maintenance of genome integrity. A prominent factor that guarantees genomic stability of cells is p53 (ref. 1).

Unexpected lack of reactivity of allogeneic anti-Ia monoclonal antibodies with MHC class II molecules expressed by mouse intestinal epithelial cells.

We have examined MHC class II molecules expression by murine gut epithelial cells using a large panel of anti-Ia antibodies. In contrast to conventional APC (i.e.

Sequence analysis reveals that the BTG1 anti-proliferative gene is conserved throughout evolution in its coding and 3' non-coding regions.

The human BTG1 gene (expressing an anti-proliferative function) is an evolutionarily conserved gene homologous to the murine PC3/TIS21 genes. Here, we report the cloning and sequencing of the murine BTG1 coding region and chicken BTG1 cDNA. The putative human and mouse BTG1 proteins are 100% identical; the chicken BTG1 cDNA contains an open reading frame of 170 amino acids with a 91% identity to its human and murine counterparts.

Class-specific suppression of human B cell maturation by IgA-binding factors.

IgA-binding factors (IgA-BFs) were prepared by chromatography on Sepharose 4B beads covalently linked to dimeric and polymeric monoclonal IgA1 from supernatants of peripheral blood mononuclear lymphocytes (PBMC) and human B cell lines incubated in serum-free medium. Receptors for IgA, as revealed by the binding of biotinylated monoclonal IgA1, were expressed on monocytes, T-enriched and T-depleted lymphocytes. IgA-BFs or control eluates were added to pokeweed mitogen (PWM)-stimulated PBMC cultures, and their effects on the terminal differentiation of polyclonally activated human B cells were assessed by enumeration of intracytoplasmic IgM-, IgG- or IgA-containing cells.

Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice.

After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads.

Production of auto-anti-idiotypic antibody during the normal immune response. IX. Characteristics of the auto-anti-idiotype antibody and its production.

Using hapten-reversible inhibition of plaque formation as an assay for auto-anti-idiotype antibody (anti-Id) and as a means for following idiotype (Id) expression, we have obtained evidence that following immunization with trinitrophenyl (TNP) conjugates (a) there are differences in Id expression in the anti-TNP antibody response to different TNP conjugates although there is some overlap; (b) different strains, although showing some differences in Id expression, tend to produce cross-reactive Ids, thus no obvious allotype linked inheritance of Id expression is observed in this heterogeneous immune response; (c) the auto-anti-Id produced following immunization with TNP-Brucella abortus or TNP-Ficoll tends to be of the IgG2a and IgG2b isotypes.

Suppression of the late stages of mitogen-induced human B cell differentiation by FC gamma receptors (FC gamma R) released from polymorphonuclear neutrophils.

During short incubation in serum-free medium, polymorphonuclear neutrophils (PMN) release soluble material that can be characterized as receptors for Fc IgG (Fc gamma R) on the following evidence: it agglutinates erythrocyte-IgG antibody (EAG) complexes, it prevents the binding of EAG to EAG-rosette-forming cells, and it binds to EAG-rosette-forming cells after modulation of their Fc gamma R, allowing the formation of 'passive' rosettes. These Fc gamma R were isolated by affinity chromatography on sepharose 4B-IgG. This material was shown to interfere with the differentiation of peripheral blood B cells into Ig-secreting cells in cultures stimulated by pokeweed (PWM) or Nocardia opaca (NOC) extracts.

Distinct functions of surface receptors in the induction of neutrophil-mediated cytotoxicity.

The respective roles of cell surface receptors were studied in a model of cell-mediated cytotoxicity using 51Cr-labelled chicken erythrocytes as target cells and human polymorphonuclear neutrophils (PMN) as effector cells. The attachment of the targets to PMN, demonstrated by rosette formation, was achieved by PMN surface receptors for C3 or for Fc IgG. No receptors for Fc IgM could be demonstrated.

Suppression of mitogen-induced peripheral B cell differentiation by soluble Fc gamma receptors released from lymphocytes.

Soluble receptors for FcIgG released from unstimulated human peripheral blood lymphocytes were isolated by affinity chromatography on Sepharose 4B-IgG. This material was shown to interfere with the differentiation of peripheral blood B cells into Ig-secreting cells in cultures stimulated with pokeweek or Nocardia opaca extracts. Neither cell viability nor [3H]thymidine incorporation were altered, but the number of Ig-containing cells and that of Ig-secreting cells were decreased.

Active and passive re-expression of Fc gamma receptors on human lymphocytes.

Modulation of receptors for IgG (Fc gamma R) on human lymphocytes was induced by the interaction with erythrocyte-IgG antibody (EAG) complexes followed by incubation at 37 degrees C. The re-expression of Fc gamma R could be achieved by two independent processes. (a) Active synthesis, susceptible to inhibition by puromycin or cycloheximide was shown to peak 4 to 6 h after removal of EAG complexes; it required addition of at least 2% fetal calf serum.

[Human lymphocyte receptors for the Fc ends of IgG].

Receptors for Fc IgG can be demonstrated by the binding of aggregated IgG or erythrocyte-IgG antibody complexes (EAG) onto subsets of B, T and "nul" lymphocytes. Among such cells are the effectors of antibody-dependent cell-mediated cytoxicity, and suppressor T cells. The binding of insoluble complexes induces a reversible modulation of the receptors associated with impaired proliferative T cell responses and transient inhibition of IgM receptors expression by adjacent T cells.

Human T lymphocyte receptors for IgM: control by IgG-binding lymphocytes.

The capacity of human peripheral blood lymphocytes to bind antigen-IgG or antigen-IgM-antibody complexes was investigated using a rosette technique with ox erythrocytes (E) coated with rabbit IgG (AG) or IgM (AM) antibodies. EAM rosette formation was achieved only in suspensions pre-incubated for 24 h at 37 degrees C. Addition of either EAM or EAG complexes to the culture medium was shown to prevent the formation of EAM rosettes.

[Prognostic value of delayed-hypersensitivity skin tests and rosette studies in acute non-lymphoid leukemias].

Delayed hypersensitivity skin reactions to Tuberculin and Candidin were studied in 28 patients with non lymphoid acute leukemias. The reactions were found negative in most patients during blastic crises, whereas delayed skin reactions to Candidin were positive during remissions. The possible prognostic significance of the depressed delayed hypersensitivity response in such patients deserves further studies.

Study of human T and B lymphocytes with heterologous antisera. IV. Subpopulations in tonsil and adenoid cell suspensions.

Mononuclear cells from eighty-seven human tonsils and fourteen adenoids were examined for T and B cells and their subpopulations. Forty six percent of the tonsil cells were killed in the presence of C by an antiserum specific for T cells and 41.7% were able to form E rosettes.

Contribution of lymphocytes bearing Fcgamma receptors to PHA-induced cytotoxicity.

Lymphocytes participating in PHA-induced lysis of chicken erythrocytes were characterized by means of cell fractionation methods. Selective depletion of, or enrichment in, E-rosetting cells indicated that the effector cell population was heterogenous, consisting of both T and non-T lymphocytes. Most effector cells, however, were shown to bear Fcgamma receptors detected by the formation of erythrocyte-antibody (EA) rosettes, but to lack C3 receptors.

Presence of "La-like" antigens on human T lymphocytes bearing receptors for IgG.

Human peripheral blood T cells bearing receptors for the Fc portion of immunoglobulins were characterized by the formation of double rosettes with sheep red blood cells and IgG-coated chicken erythrocytes (EA). Treatment of cells by anti-"Ia-like" antisera inhibits the binding of EA. Inihbition appeared to be specific since anti-HLA-A and HLA-B antibodies did not inhibit the formation of EA rosettes, whereas F (ab')2 fragments of anti-Ia-like IgG were found to be as potent inhibitors as the whole IgG.

T-dependence of human B lymphocyte proliferative response to mitogens.

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present.