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Biomedical subjects

L Forni

Publications and source records attributed to L Forni.

71 records · Page 4Linked to original sources
PubMed1976

IgD receptors of lymphoid cells.

While present in normal human serum in very low amounts and undetectable in sera of non-human primates as well as of mice, IgD is found on the surface of the majority of B lymphocytes in all the above mentioned species. Lymphocytes which carry IgD on their membrane also have IgM. The two molecules are present in relative amounts that can be very different in different cells. Both IgM and IgD of a single cell are the actual product of the cell itself. They have the same light chain and, more importantly, the same combining site and idiotype. IgD/IgM bearing lymphocytes are the majority of all B lymphocytes in spleen, lymph nodes and Peyer's patches, whereas in bone marrow they account for half of the immunoglobulin positive cells. Although the percentage of double IgD/IgM cells is very similar in different tissues, the total amount of IgD, as well as the relative amounts of IgD and IgM as detected by biochemical methods varies. In fact, lymph nodes, and even more Peyer's patches are much richer than spleen in cells having levels of IgD higher than those of IgM; conversely, in the bone marrow, all the positive cells have very low levels of IgD. In ontogeny, as in evolution, IgD appears after IgM: in human foetuses IgD bearing cells are not detectable before 13 weeks of gestation, and in the mouse they appear only after birth. IgD receptors seem to disappear from B cells which undergo maturation to secretion, as indicated by the fact that only a proportion of IgM secreting plasma cells show membrane IgD. IgD is never found on the membrane of IgG-containing cells, and also lymphocytes bearing simultaneously IgD and IgG are very rare, and it might well be that for these cells, the double expression for short periods of time does not actually correspond to simultaneous synthesis.

Antibodies, Anti-Idiotypic↗
PubMed1974

IgM-producing tumors in the BALB-c mouse: a model for B-cell maturation.

Five adjuvant induced BALB/c tumors producing IgM-McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781-were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10-25-h stimulated normal B cells, 3469 cells resemble 20-35-h stimulated B cells, TEPC 183 cells resemble 45-65-h stimulated B cells, Y 5781 cells resemble 80-110-h stimulated B cells, and McPc 774 cells resemble 100-130-h stimulated B cells.

Animals↗
PubMed1973

Immunoglobulin D as a lymphocyte receptor.

A large proportion of the human peripheral blood lymphocytes of adults and newborns having IgD were found also to have IgM on their membranes and vice versa. A few lymphocytes had one of these classes only. IgD and IgM could be capped independently on the same cell. The possibility that IgD was acquired by a cytophilic process was excluded by the finding that IgD-bearing cells were of one light chain type only, and by the direct demonstration of reappearance of IgD on the lymphocyte membrane during incubation in an IgD-free culture medium. On the basis of these findings, it is proposed that IgD functions as a lymphocyte antigen receptor.

Adult↗
PubMed1973

Blocking and redistribution ("capping") of antigen receptors on T and B lymphocytes by anti-immunoglobulin antibody.

Antigen-binding T and B lymphocytes were studied by combined autoradiography and immunofluorescence; mouse spleen lymphocytes binding the antigens, [(125)I]MSH or [(125)I]TIGAL, were incubated with rhodamine-labeled anti-Ig reagents or with a rhodamine-labeled IgG fraction of anti-theta serum. B cells were identified as Ig+ or theta-, T cells as Ig- or theta+. It was found that: (a) 20% (1-2 mo after priming) to 30% (3.5-4 mo after priming) of the antigen-binding cells were T cells. (b) The range of antigen molecules bound by B and T cells was similar. (c) Binding of antigen to B and T cells was inhibited by polyvalent anti-Ig, anti-micro, or anti-L reagents. Binding to T cells was more readily inhibited than to B cells. Normal rabbit serum, antimouse lymphocyte serum, or anti-theta did not inhibit antigen binding. (d) When Ig at the surface of B cells was induced, by noninhibiting concentrations of anti-Ig reagents, to redistribute into polar caps and the cells subsequently exposed to [(125)I)antigen under noncapping conditions, the [(125)I]antigen silver grains were distributed in caps superimposed on the Ig fluorescent cap. Of crucial importance, antigen was found in cap in the same proportion of T cells as B cells. Significant capping of antigen receptors was not induced in B or T cells with normal rabbit serum or by anti-Ig reagents absorbed with mouse Ig. The main conclusions of this series of experiments using direct visualization of antigen-binding B and T lymphocytes is that T cells have antigen-specific receptors, probably of IgM nature, and that the number of these receptors appears to range in the order of thousands.

Animals↗
PubMed1970

Immunoglobulin spots on the surface of rabbit lymphocytes.

Small and medium lymphocytes from the peripheral blood and lymphoid tissues of the rabbit react in suspension with antibodies directed against different immunoglobulin determinants. Through immunofluorescence, it was possible to show that numerous discrete spots on the surface of the positive lymphocytes carry immunoglobulin molecules. The positive lymphocytes are about one-half of all lymphocytes in the different preparations; thymus lymphocytes are all negative. With antisera specific for rabbit IgM as well as with antisera directed against allotypic determinants specific for IgM or IgG, it was possible to show that about nine-tenths of the immunoglobulin-positive lymphocytes carry IgM molecules on their surface. With antisera directed against a- and b-locus determinants, it was also possible to demonstrate that both heavy and light chains were present in the surface immunoglobulins. Furthermore, in animals which were heterozygous at the a or the b locus, it was found that each lymphocyte had immunoglobulins synthesized under the influence of only one of two alleles. A very small proportion of lymphocytes could be shown to have a specific surface reaction with one antigen (horse ferritin); the proportion of these cells increased very much after immunization.

Animals↗
PubMedDate not supplied

Antigen-specific and -non-specific regulatory influences of antibody in immune responses are determined by variable region properties.

The regulatory effects of a constant titre of anti-sheep erythrocyte (SRBC) antibodies collected during primary and secondary responses and separated according to class, as well as monoclonal antibodies of the same isotypes, were compared by studying the specific and total plaque-forming cell (PFC) responses to the simultaneous administration of antigen. Polyclonal secondary IgG1 antibodies were found unique in their ability to suppress completely specific PFC responses. Polyclonal secondary antibodies of other IgG subclasses, polyclonal primary IgG1 and monoclonal IgG1 antibodies, all were found at the same titre either totally ineffective or mediating very litte suppression. Primary polyclonal IgM antibodies were also found much superior to monoclonal antibodies and to secondary polyclonal IgM antibodies in their ability to enhance specific responses and largely augment the total number of Ig PFC in the spleen. While these results are most easily interpreted by postulating a primary determination of regulatory properties by V-regions, we could not find evidence for "allotype-restriction" of these effects.

Animals↗
PubMedDate not supplied

Natural lymphocyte activation in postnatal development of germ-free and conventional mice.

The degree of activation of B and T cells in the developing spleen during postnatal life was studied in germ-free (GF) and specific-pathogen-free (SPF) BALB/c mice of the same breeding stock. We found that the progeny of GF mothers up to 3 weeks of age contain higher numbers of activated splenic cells than baby SPF mice, thus suggesting qualitative differences in maternally-derived antibodies. This "advantage" of GF mice is also indicated by an anticipated maturation of the splenic lymphoid compartment and is reflected in higher frequencies of B and T lymphocytes in adult life. In both kinds of mice, the frequency of activated cells is very high at birth and then declines, reaching minimal values by 4 weeks of age. Later, activated B cells increase sharply in SPF mice, suggesting polyclonal activation mediated by bacterial products. Results are discussed on the basis of the mutual influences between B and T cells in the establishment of a functional network.

Animals↗
PubMedDate not supplied

Strain differences in the postnatal development of the mouse splenic lymphoid system.

Four strains of mice, CBA/J, BALB/c, C57BL/6J and B10.BR, were studied for cellular composition of the developing spleen in postnatal life. Considerable strain differences were found in the absolute numbers of splenic lymphoid cells at various ages, the frequencies of B and T cells, the L3T4/Lyt-2 ratio and the time of appearance of IgD and class II antigen on B cells. These observations are discussed in view of strain differences described for the acquisition of immune responsiveness and for susceptibility to tolerance induction in neonates. Finally, it was found that the expression of I-E antigen is delayed compared to that of I-A in ontogeny and possibly during B-cell differentiation as well.

Animals↗
PubMedDate not supplied

From the mechanisms of lymphocyte activation to internal activity in the immune system.

The principles of lymphocyte activation were summarized for all three sets of immunocompetent cells: B cells, cytotoxic cells and helper T lymphocytes. They were then used to derive the basic mechanisms and specificities which drive internal activity in the normal immune system and which select available antibody repertoires. It was postulated that "natural antibodies" are induced by "natural helper cells" and are selected on the basis of their idiotypic profiles, which are complementary to available T-helper-cell repertoires. "Natural idiotypes" would then carry idiotopes similar to MHC epitopes, the predominant germ-line specificity of T-cell repertoires.

Animals↗
PubMedDate not supplied

T-cell-dependent modulation of the polyclonal B-lymphocyte responses in normal spleen cell cultures stimulated by lipopolysaccharide.

The in vitro polyclonal B-cell proliferative and plaque-forming cell (PFC) responses to the T-independent (TI) mitogen lipopolysaccharide (LPS) are increased by the addition of normal syngeneic splenic T cells. Normal irradiated Lyt-2- T cells also alter the IgG subclass distribution from the typical predominance of IgG3 and IgG2b PFC to the appearance of IgG1, IgG2a and IgA PFC in T-cell-depleted spleen cell (SC) cultures. Furthermore, secondary LPS blast cultures yield increased PFC responses when co-cultured which syngeneic fresh normal T cells which, even in the absence of mitogen, induce PFC responses in such activated B cells. As LPS blasts induce normal syngeneic T cells to proliferate and significant numbers of L3T4+ blast cells are found in LPS-stimulated normal spleen cell cultures, we conclude that T cells actively participate in the regulation of these responses. The significance of these findings for the regulation of TI responses in vivo by "autoreactive" T cells is considered.

Animals↗
PubMedDate not supplied

The membrane receptor complex regulating induction and clonal expansion of normal murine B lymphocytes.

Induction of resting B lymphocytes results from the interaction of competent ligands or helper cells with "triggering receptors." Subsequent clonal expansion and performance are thought to be regulated by the interaction of selective growth or maturation factors with specific receptors on induced B cells. A set of membrane molecules of B lymphocytes, including IgM, IgD, IA, IE, lipopolysaccharide receptors, receptors for Fc and C3b, and other non-immunoglobulin structures recognized by some antiidiotypic antibodies, display ligand-induced relationships. Functional studies also indicate that this group of molecules functions as a complex that regulates delivery of inductive signals, the expression of growth and maturation receptors, and/or the outcome of the interactions of these receptors with the corresponding factors.

Animals↗