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Biomedical subjects

I Scher

Publications and source records attributed to I Scher.

At least 109 records · Page 6Linked to original sources
PubMed1977

Studies on non-H-2 linked lymphocyte activating determinants. I. Description of the cell type bearing the Mls product.

The non-H-2 linked, lymphocyte activating determinants (LADs), which are coded by the minor (histocompatibility) lymphocyte stimulating locus (Mls), were detected on B lymphocytes, but not on immunoglobuin (Ig) negative or on theta positive T lymphocytes. These determinants, like the complement receptor and surface IgD, develop late in neonatal life. Thus, the Mls coded LADs mark a population of B lymphocytes which are not present in the spleens of newborn to 2-week-old mice. Studies of B lymphocytes derived from the spleens of adult mice indicated that the cells bear the Mls coded LADs have a high density of surface Ig and possess the complement receptor.

Animals↗
PubMed1977

Murine B lymphocyte heterogeneity: distribution of complement receptor-bearing and minor lymphocyte-stimulating B lymphocytes among cells with different densities of total surface Ig and IgM.

The distribution of complement receptor-bearing (CR+) and minor lymphocyte-stimulating (Mls)-defined lymphocyte-activating determinants (LAD) among B lymphocytes with different densities of total surface immunoglobulin (sIg) and sIgM was determined. B lymphocytes that bore intermediate densities of sIg and low densities of sIgM had the highest frequency of CR+ cells and were the most active in expressing Mls-defined LAD. The distribution of these and other surface markers on B-lymphocyte subpopulations is discussed.

Animals↗
PubMed1976

B-lymphocyte heterogeneity: ontogenetic development and organ distribution of B-lymphocyte populations defined by their density of surface immunoglobulin.

The density of total Ig and of IgM, IgG1, IgG2, and IgA on the surface of adult murine splenic B lymphocytes was measured using the technique of rapid flow microfluorometry. In addition, the density of total surface Ig and of IgM on B lymphocytes derived from adult bone marrow, lymph nodes, and Peyer's patches, and from neonatal spleen was determined. Adult spleen and lymph node B lymphocytes are characterized by the presence of a large population of cells with a low-to-intermediate density of total surface Ig, which is seen as a peak in the fluorescence profiles when these cells are labeled with fluorescein-conjugated (F1) anti-Ig. This peak is not detected when neonatal spleen or adult bone marrow are examined; the development of this peak among spleen cells occurs during the first 4 wk of life. Although the characteristic fluorescence intensity peak is not seen when adult spleen cells are labeled with Fl anti-mu, changes in the density of surface IgM do occur during the first few weeks of life and are detected as a decrease in the frequency of cells which have relatively large amounts of surface IgM. The differences seen in the fluorescence patterns of adult spleen cells labeled with Fl anti-Ig and Fl anti-mu may be due to the appearance of IgD on the surface of mature splenic B lymphocytes. This is supported by the similarity of the fluorescence profiles of adult bone marrow cells stained with Fl anti-Ig and Fl anti-mu, as the latter population of cells is reported to lack surface IgD.

Age Factors↗
PubMed1976

X-linked B-lymphocyte defect in CBA/N mice. III. Abnormal development of B-lymphocyte populations defined by their density of surface immunoglobulin.

CBA/N mice have an X-linked defect in B-lymphocyte function characterized by a failure to respond to certain thymus-independent antigens. When studied by rapid flow microfluorometry, adult CBA/N splenic B lymphocytes labeled with either fluorescein-conjugated (Fl) anti-Ig or Fl anti-mu had fluorescence profiles which were considerably different from those of B lymphocytes derived from normal mice. By studying progeny of crosses of CBA/N and normal mice, it was shown that the abnormal fluorescence profiles of CBA/N B cells were determined by an X-linked gene. The fluorescence profile of adult CBA/N splenic B lymphocytes labeled with anti-mu were very similar to the patterns of neonatal normal and of neonatal CBA/N splenic B lymphocytes suggesting that the defect of CBA/N mice is due to a failure in the development of a mature B-lymphocyte population. The fluorescence profiles of adult CBA/N splenic B lymphocytes labeled with Fl anti-Ig also had immature characteristics in that the frequency of cells with large amounts of surface immunoglobulin was increased in comparison to that of normal strains and the population of cells with low-to-intermediate density of total surface immunoglobulin, which appear characteristic of normal adult splenic B lymphocytes, was markedly diminished.

Animals↗
PubMed1976

Functional characterization of a naturally occurring antibody cytotoxic for a subpopulation of splenic T cells.

Sera from old (greater than 6 months) New Zealand Black (NZB) mice were shown to contain an IgM antibody which was cytotoxic for thymus-derived (T) lymphocytes in the presence of rabbit complement. This antibody in the presence of complement markedly decreased the response of normal spleen cells to the T cell mitogen concanvalin A (Con A) but not to another T cell mitogen phytohemagglutinin-P (PHA-P). Responses of these treated cells to the polyclonal B cell mitogens, bacterial lipopolysaccharide (LPS), and polyriboinosinic-polyribocytidylic acid (poly[I]-poly[C]) were unimpaired. This naturally occurring NZB antibody was different from conventional anti-theta serum which abolished the response to both PHA-P and Con A. Moreover, the NZB serum affected spleen cells from both theta-C3H and theta-AKR mice. The ability of such serum to influence, differentially, Con A reactive cells as opposed to PHA-P-reactive cells, suggest that the NZB antiserum recognizes a subpopulation of T lymphocytes.

Animals↗
PubMed1976

Cellular mechanism of endotoxin unresponsiveness in C3H/HeJ mice.

B cells from C3H/HeJ mice fail to respond to an endotoxin (LPS K235) which is mitogenic for normal mice including the closely related C3H/HeN strain. The cellular basis for this unresponsive state has been investigated. The C3H/HeJ mice have normal numbers of B cells, which are capable of normal responses to other B cell mitogens, such as polyinosinic acid (Poly I). Addition of normal macrophages or spleen cells fails to reconstitute the normal response. Furthermore, neither macrophages nor spleen cells from the C3H/HeJ strain suppress the normal C3H/HeN spleen cells. Finally, spleen cells enriched for B cells by the removal of macrophages or T cells demonstrate the same differences in responsiveness to LPS. These results indicate that LPS unresponsiveness is a defect of the B cell itself and not due to suppressor cells or the absence of helper cells. When LPS is added to Poly I-stimulated cultures, there is additional enhancement of the response of normal C3H/HeN spleen cells. However, LPS causes a dose-dependent suppression of the Poly I response of C3H/HeJ spleen cells. This suppression is dependent on the time of addition of LPS to the Poly I-stimulated cultures. These data are interpreted as indicating that the binding of LPS to the membrane of C3H/HeJ B cells results in their inactivation or suppression, and that this is the basis of LPS unresponsiveness in this mouse strain.

Animals↗
PubMed1976

In vitro studies of the genetically determined unresponsiveness to thymus-independent antigens in CBA/N mice.

The X-chromosome-linked B lymphocyte defect of CBA/N mice has been studied in vitro by comparing the ability of (CBA/N X DBA/2)F1 (X-/X- X X+/Y) male (X-/Y) and female (X-/X+) spleen cells to respond to the thymus-independent antigen DNP (or TNP)-AECM-Ficoll. (CBA/N X DBA/2)F1 male spleen cells failed to generate significant in vitro anti-TNP antibody responses to DNP- or TNP-AECM-Ficoll, in contrast to spleen cells from F1 female (X-/X+) mice which responded normally to these T-independent antigens. Spleen cells from male F1 mice responded almost as well as F1 female cells to the thymus-dependent antigen, TNP-sheep red blood cells (TNP-SRBC) in vitro. Adding F1 male cells to F1 female cells failed to reduce the response of the latter to DNP-AECM-Ficoll, suggesting that the inability of F1 male cells to respond was not due to active suppression. The response of F1 male spleen cells to TNP-SRBC was not impaired by adding high concentrations of TNP-AECM-Ficoll indicating that the mechanism of unresponsiveness was not tolerance induction in all TNP-specific precursors. Lymphocytes from F1 male mice were capable of forming anti-TNP antibody after stimulation with lipopolysaccharide (LPS) in high concentrations; DNP-AECM-Ficoll had no effect on this polyclonal response. B lymphocytes from mice bearing only the X-chromosome of the CBA/N strain thus display a profound defect in B cell activation. This functional defect may represent either an inability of the defective B cells to be activated by thymus-independent antigens or the absence of a sub-class of B cells which respond to thymus-independent antigens.

Animals↗
PubMed1976

Studies on non-H-2-linked lymphocyte-activating determinants. II. Nonexpression of Mls determinants in a mouse strain with an X-linked B lymphocyte immune defect.

Minor lymphocyte-stilulating (MIs) coded non-H-2-linked lymphocyte-activating determinants (LADs) are present on a late developing subpopulation of murine B lymphocytes. Spleen cells derived from CBA/N mice, a strain with an X-linked defect in B cell function, failed to stimulate a response in MIs-defined mixed lymphocyte reactions (MLRs) with H-2 identical CBA/J or C3H/N responder spleen cells. However, both CBA/J and C3H/N spleen cells induced significant responses in CBA/N responder spleen cells. The inability of CBA/N cells to induce an MIs-defined response was not due to the presence of the nonstimulatory MIsb genotype, since spleen cells of immunologically normal F1 mice derived from crosses of CBA/N and C3H/N mice were stimulatory in MLRs for C3H/N responder cells. Immunologically abnormal CBA/N female x C3H/N male) F1 male mice, which are hemizygous for the CBA/N X chromosome, were also unable to induce a response in MIs-defined MLRs. Although the MIs coded LADs are not X linked in immunologically normal mouse strains, these data indicate that the failure of CBA/N mice to functionally express the MIs-coded LADs is X linked. This characteristic was not secondary to the presence of suppressor cells and is most likely related to the absence of a late developing (mature) subpopulation of B lymphocytes in these mice.

Animals↗
PubMed1976

In vitro responses of CBA/N mice: spleen cells of mice with an X-linked defect that precludes immune responses to several thymus-independent antigens can respond to TNP-lipopolysaccharide.

Spleen cells from CBA/N mice with an X-linked B cell defect were examined for their ability to form antibody in vitro after stimulation with the T-independent antigen TNP-LPS. In contradistinction to their failure to respond to some conventional T-independent antigens such as type III pneumococcal polysaccharide or DNP-AECM-Ficoll, spleen cells from (CBA/N X DBA/2)F1 male mice were able to make a specific anti-TNP PFC response after culture with TNP-LPS. Their response differed from that of phenotypically normal (CBA/N X DBA/2)F1 female littermate spleen cells in that more TNP-LPS was required to elicit the peak anti-TNP response and the anti-TNP antibody secreted by F1 male cells was of lower avidity than that of F1 female cells. The polyclonal antibody response to unsubstituted LPS did not differ substantially between normal and defective B cells. Tnymus-derived cells were not required for the TNP-LPS response by either F1 male or female cells. We conclude that CBA/NB cells can respond to certain T-independent antigens that are able either to induce a very strong activating signal upon ligand-surface receptor interaction and/or to stimulate immature B cells (with a characteristic high surfact immunoglobulin profile) which fail to respond to antigens like DNP-AECM-Ficoll.

Animals↗
PubMed1976

Selective inhibition of lymphocyte responsiveness to phytohaemagglutinin in patients with Reiter's syndrome.

The influence of synovial fluid from four patients with Reiter's syndrome on lymphocyte responsiveness was studied. On synovial fluid was found which specifically depressed the responsiveness of lymphocytes from patients with Reiter's syndrome to the non-specific mitogen phytohaemagglutinin (PHA). The ratio of the responsiveness of lymphocytes cultured in the presence of foetal calf serum (FCS), compared to those incubated in the Reiter's synovial fluid, was used as a measure of the depression induced by the Reiter's synovial fluid. The mean ratio for eight normals stimulated with PHA was 0-70 (range 0-35-0-96), while for eight patients with Reiter's syndrome, it was 0-13 (range 0-07-0-19). Similar studies done with concanavalin A (con A) showed no difference between lymphocytes from normals (0-73) or patients with Reiter's syndrome (0-67). Chromatography of the Reiter's synovial fluid on a Sepharose 4-B column resulted in the separation of three major fractions, one of which exhibited the inhibitory activity. When this active fraction was absorbed with Reiter's lymphocytes, a loss of the inhibitory activity of the fraction was seen. A similar absorption with normal lymphocytes had no effect. These studies demonstrate that a factor present in the synovial fluid of a patient with Reiter's syndrome reacted specifically with lymphocytes from patients with Reiter's disease and not with lymphocytes from normals. The interaction of this factor with lymphocytes from patients with Reiter's syndrome inhibited the responsiveness of these lymphocytes to PHA but not to con A.

Adult↗
PubMed1975

Abnormal ratio of membrane immunoglobulin classes in mice with an X-linked B-lymphocyte defect.

CBA/N mice have an X-linked genetic defect in B-lymphocyte function manifested by inability to make antibody responses to T-independent antigens. Plasma membrane immunoglobulin (Ig) on spleen, lymph node, and Peyer's patch cells was analyzed by lactoperoxidase-catalyzed iodination, NP-40 extraction, specific immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These studies indicated that the X-linked immune defect was associated, in all three cell types, with a decrease in the ratio of cell membrane IgD analog to cell membrane IgM. This suggests either that IgD analog may be important in initiation of T-independent antibody responses or that CBA/N mice lack a subpopulation of B cells specialized to respond to T-independent antigens, and that these cells are relatively rich in plasma membrane IgD analog.

Animals↗
PubMed1975

X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect.

The mechanisms underlying the X-linked thymus-independent (B) lymphocyte functional defect in the CBA/N (CN) mice and their F1 progeny were studied. Immune defective mice were unable to respond to the T-independent antigen 2,4-dinitrophenyl-lysyl-derivative of Ficoll (DNP-lys-Ficoll) but were able to form antibody against the highly cross-reactive hapten (trinitrophenyl) when it was coupled to an erythrocyte carrier. Immune defective CN X DBA/2N (DN) F1 male mice, which do not normally respond to T-independent antigens, were able to respond to both polyribosinic-polyribocytidylic acid and DNP-lys-Ficoll after the administration of CN X DN F1 female spleen cells even if these cells had been depleted of T lymphocytes. In addition, it was shown that the inability of the CN mice and their F1 progeny to respond to T-independent antigens was not due to an intrinsic abnormality of their microenvironment or the suppressive actions of a T lymphocyte. Our data present evidence that the X-linked defect in the CN mice is due to an intrinsic defect in B-lymphocyte development.

Animals↗
PubMed1975

X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells.

A study of the composition and functional properties of spleen cells from the immune deficient CBA/HN mice and their F1 progeny is reported. While abnormalities were seen in both the numbers and function of thymus-independent (B) lymphocytes, all studies involving thymus-dependent (T) lymphocytes were normal. The X-linked nature of the immune defect in these mice was therefore attributed to abnormal or absent B lymphocytes. The possible nature of this defect and the similarity of the immune defect in these mice to certain human X-linked immunodeficiency diseases are discussed.

Animals↗