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Biomedical subjects

L Forni

Publications and source records attributed to L Forni.

At least 55 records · Page 3Linked to original sources
PubMed1981

Effect of anti-delta antibodies on clonal expansion and maturation of B lymphocytes.

The effect of a monoclonal anti-delta antibody on the in vitro B cell response to the B cell mitogen lipopolysaccharide (LPS) has been studied. Titration of anti-delta antibody in mass cultures stimulated by LPS resulted in a dose-dependent reduction of thymidine incorporation. IgM and IgG plaque forming cell (PFC) responses were poorly affected at high concentration, and slightly increased at low concentrations of anti-delta antibody. By limiting dilution analysis it was shown that anti-delta antibody inhibit 30-50% of LPS-reactive B cells to grow as IgM secreting clones, while increasing the average size of clones that grew in the presence of anti-delta as compared to control cultures. Anti-delta also results in increased frequencies of IgG secreting clones. By immunofluorescence it was possible to show the presence of a higher relative number of cells containing immunoglobulin as an effect of anti-delta antibodies. Observations made at early times of culture indicate that the cells that do not proliferate in the presence of anti-delta undergo an early maturation to secretion. Experiments performed on LPS blasts suggest that the effects of anti-delta on cell proliferation require the presence of antibodies at early times in the response, while the effects on maturation can be manifested during clonal development. The relevance of membrane IgD and of the IgM-to-IgD ratio in the maintenance versus exhaustion of the clone is discussed.

Animals↗
PubMed1981

The enhancement of antibody response by IgM antibodies is dependent on antigen-specific T helper cells.

The enhancement of antibody responses by IgM antibodies administered with low doses of antigen has been studied in a T-dependent (SRBC) and an T-independent (alpha 1,6 dextran) system. It has been found that IgM anti-SRBC antibodies do not enhance a SRBC response in nude mice. The T-cell dependency was also directly demonstrated by showing the effect of IgM on T-cell priming in transfer experiments. The simultaneous injection of antigen and IgM antibody also induced a polyclonal increase of IgM, PFC, which was not due to a non-specific "adjuvant" effect of IgM, as we could not detect a similar effect on an ongoing response to HRBC in mice simultaneously given SRBC and IgM anti-SRBC antibodies. The specificity of the helper cell for either the antibody or the antigen was investigated in a response to alpha 1, 6 dextran, in which we could demonstrate antibody-specific helper T cells, but no antigen-specific help. We have found that IgM anti-dextran antibodies do not enhance and rather suppress the response of normal, high-responder mice, to dextran, suggesting that the T cells mediating the "19S enhancement" are antigen-specific. The magnitude of the enhancement response, as compared to the responses induced by either antigen or antibody alone, implies a synergistic mechanism, possibly involving antigen-specific and antibody(idiotype)-specific T helper cells.

Animals↗
PubMed1981

Suppression of a "recurrent" idiotype results in profound alterations of the whole B-cell compartment.

The progeny of BALB/c female mice actively immunized with the trinitrophenyl-binding myeloma protein MOPC460 and producing anti-idiotypic antibodies during pregnancy were compared with mice born of normal mothers for several characteristics of B lymphocytes and their precursors. In all cases, maternal anti-idiotypic immunity resulted in the suppression of the expression of that idiotype by immunocompetent cells in the progeny, as shown by limiting-dilution analysis in single clones of mitogen-reactive IgM-secreting cells. At critical concentrations of circulating maternal antibodies, suppression of the antibody idiotype was found to be accompanied by a large increase in the total number of mature small B lymphocytes. This increase can be accounted for by the selective expansion of B cells bearing nonimmunoglobulin surface structures crossreactive with a MOPC460 idiotope recognized by a monoclonal antibody. In addition, the large majority of newly formed mature B lymphocytes, as well as a large fraction of immunoglobulin-negative cells in the bone marrow of suppressed mice, bear such nonimmunoglobulin MOPC460 crossreactive determinant(s). These results suggest that the suppression of a given "recurrent" idiotype has profound consequences for a large part of the immune system.

Animals↗
PubMed1981

Genetics of a non-H-2 antigen that stimulates "unrestricted" helper T cells and MLR.

The inheritance of antigens expressed by C3H/Tif B cells that stimulate MHC-unrestricted helper T cells from C3H/HeJ was investigated. F1 hybrids between C3H/HeJ and C3H/Tif and 39 C3H/HeJ X F1 backcross mice were characterized as to the ability of their spleen cells to stimulate a proliferative C3H/HeJ T helper cell response and to respond to helper cell activity by the development of polyclonal plaque-forming cell responses. Backcross progeny wee also typed for the following markers segregating in this cross: 1) Responsiveness to the B cell mitogen lipopolysaccharide (LPS); 2) LyM-1 allotype; 3) antigen(s) stimulating a primary non-H-2 MLR between these strains, previously ascribed to Mls locus differences, 4) expression of target antigens for cytotoxic T cells raised in the same strain combination. The antigen(s) recognized by helper cells and those stimulating primary MLR are controlled by autosomal gene(s) and segregate as a single trait. These antigens, however, are not encoded in genes linked to either the Lps or the Mls loci, and are not recognized by cytotoxic T cells raised in the same strain combination.

Animals↗
PubMed1980

IgM antibodies induce the production of antibodies of the same specificity.

Injection in normal mice of IgM antibodies against sheep erythrocytes or dextran, in the form of an immune serum depleted og IgG, induces direct plaque-forming cells of the same specificity as the injected antibodies. The response is 10--70 times higher than the background plaque-forming cell titer of untreated control mice. Nanogram amounts of IgM induce a detectable response, and a ceiling is reached with a few hundred nanograms of monoclonal IgM. The inducing agent is not residual antigen: (i) treatment of the injected material and the recipients with dextranase abolishes the immunogenicity of dextran, but not the response to anti-dextran IgM; (ii) monoclonal IgM specific for sheep erythrocytes or trinitrophenyl likewise induces plaque-forming cells of the respective specificity, but variant hybridoma products (in which the light chain is that of the myeloma parent) are inactive. In normal mice, IgM-induced antibody responses were observed with antibodies to both thymus-dependent and thymus-independent antigens, but such could not be induced in athymic (nude) mice. Because the mechanism underlying this phenomenon would operate also in a normal immune response and, presumably, in the normal dynamic state of the immune system of unstimulated animals, a network regulation among the elements of the immune system itself is implied.

Animals↗
PubMed1980

Antibody directed against Friend leukemia virus stimulates DNA synthesis in a subpopulation of mouse B lymphocytes.

Goat and rat antisera directed against Friend leukemia virus (anti-FLV) were found to be B-lymphocyte mitogens stimulating DNA synthesis in these cells but not in T lymphocytes. Membrane fluorescence microscopy showed that anti-FLV reacts with a subset of B lymphocytes of which the majority express immunoglobulin mu chains. The mitogenic effect was found with all mouse strains tested including 129 and AKR. Absorption experiments with purified viruses indicated that the mitogenic effect is specific for an antigen present in murine leukemia viruses of the FMR subgroup. In absorption experiments with viable cells, the antigen involved in mitogenicity was found to be expressed on Friend erythroleukemia cell lines (4/4) and on myelomas (2/2) but not on normal thymus T lymphomas (0/2) or on rabbit or mink cells infected with BALB/c xenotropic virus. Preincubation of spleen cells with anti-gp70 antiserum inhibited the mitogenic effect of anti-FLV but not of lipopolysaccharide.

Animals↗
PubMed1978

Shared antigenic determinants by mitogen receptors and antibody molecules to the same thymus-independent antigen.

The antibody response to dextran B1355 is thymus independent, and in high responder mice, over 90% of the antibodies carry the idiotype of an alpha-1,3 binding myeloma protein (J558). The present experiments demonstrate: (a) dextran B1355 is a B-cell mitogen both in a strain which carries the J558 idiotype on antibodies and in a low-responder strain which does not express that idiotype on antibodies to dextran; (b) anti-idiotypic antibodies to J558 recognize a dextran-specific surface receptor on 10--15% of all splenic B cells in those two strains as well as in all strains so far tested; (c) as shown by inhibition experiments such surface receptors cross-react with J558, and (d) anti-idiotypic antibodies are mitogenic for spleen cells of both strains resulting in B-cell proliferation and maturation to polyclonal antibody secretion.

Antibodies↗
PubMed1978

Switch in immunoglobulin class production observed in single clones of committed lymphocytes.

Mouse spleen cells, after stimulation with lipopolysaccharide, were cloned in culture. After 4 to 5 days, the daughter cells were stained and examined for immunoglobulin class with double immunofluorescent reagents. A switch of the stained color of these cells was observed, implying a switch from imunoglobulin M to immunoglobulin G production in the progeny of a single B cell.

Animals↗
PubMed1978

An antiserum which recognizes lipopolysaccharide-reactive B cells in the mouse.

Rabbit antisera have been prepared against spleen B cells from C3H/Tif mice, high responders to lipopolysaccharide (LPS). After complete absorption on tissues of C3H/Hej mice (LPS nonresponders), such antisera specifically stain and kill (in the presence of complement) a fraction of the B cells from a number of LPS high responder strains, and fail to recognize any cells in two different LPS nonresponder strains, C3H/HeJ and C57B1/10.Sc.Cr. The ontogeny, organ and strain distribution of this B cell marker parallels LPS reactivity. Frequencies of cells stained by this antiserum correspond to the frequencies of LPS-reactive B cell precursors recently determined. This antigent(s) is expressed by LPS-activated B cell blasts but not by cells which remain small after 48 h in the presence of LPS. Removal of the cells recognized by the antisera leads to depletion of LPS-reactive cells, while enriching for reactivity to another B cell mitogen, e.g. lipoprotein.

Animals↗
PubMed1978

Genetic and functional characterization of an antiserum to the lipid A-specific triggering receptor on murine B lymphocytes.

The inheritance of responsiveness to lipopolysaccharide (LPS), and of a marker recognized in LPS-reactive cells by a heterologous antiserum, was studied in crosses between C3H/HeJ (nonresponder) and C3H/Tif (high responder) mice. F1 hybrid mice show codominant expression of these traits: (a) LPS-reactive cells are only hlaf as frequent in the hybrids as in the high responder parent; (b) the serologically defined marker is expressed in half as many cells in the hybrids as in the high responder parent. In backcross generations, both LPS responsiveness and this serological marker segregated into high, intermediate, and nonresponders. LPS or free lipid A, but not two other B cell mitogens (lipoprotein, and purified protein derivative of tuberculin), compete with the antiserum for binding to the B cell surface membrane, and are capable of completely inhibiting such binding without interfering with the binding of a-ti-Ig antibodies or complexes to Fc receptors. The addition of an IgG fraction of the antiserum to B cell cultures results in exponetial growth of the cells and in maturation to antibody secretion. This mitogenic activity is dose-depedent and absorbable on spleen cells from LPS high responder mice. Taken together, these observations suggest that this antiserum contains antibodies to the lipid A-specific triggering receptor on B lymphocytes.

Animals↗