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Biomedical subjects

S M Fu

Publications and source records attributed to S M Fu.

At least 127 records · Page 7Linked to original sources
PubMed1979

Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors.

Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig.

Antibody Formation↗
PubMed1979

Human cell lines containing Epstein-Barr virus but distinct from the common B cell lymphoblastoid lines.

A group of very similar cell lines was established from peripheral blood or bone marrow of 12 patients with a variety of disorders. The cells in these cell lines were uniform and round in shape. They grew as single-cell suspensions or as aggregates of small numbers of cells in stationary culture. The most striking characteristic of these lines was the lack of cells with surface immunoglobulin or with demonstrable immunoglobulin synthesis. This lack of immunoglobulin synthesis and their special growth characteristics distinguished them from the lymphoblastoid B cell lines previously described. The cells of these unusual cell lines had strong Fc receptors and C3 receptors and expressed Ia antigens. They did not form rosettes with sheep erythrocytes and did not have detectable levels of terminal deoxynucleotidyltransferase. They did not secrete lysozyme and failed to stain for peroxidase. The presence of the Epstein-Barr virus nuclear antigen in the cells indicated the presence of Epstein-Barr viral genome. The possibility that these cells represent some type of precursor cell in the B cell lineage is discussed, but the exact cellular origin remains to be ascertained.

Antigens, Viral↗
PubMed1979

Induction of human antibody responses in vitro with emphasis on allogeneic helper factors.

Systems have been developed for the reproducible production of antigen-specific plaque forming cells for both tonsillar and peripheral blood B cells. Allogeneic helper activity was an essential supplement and monocyte removal was important, especially in the peripheral blood situation. Highly active allogeneic helper factors could be obtained from undirectional MLC supernatants which aided the proeuction of antigen-driven plaques. These factors also caused a polyclonal activation of B lymphocytes. A number of clinical applications of the above system were described. A defect in the T cells of patients with chronic lymphocytic leukemia with respect to the generation of helper activities was delineated.

Antibody Formation↗
PubMed1979

Poor mixed lymphocyte reaction stimulatory capacity of leukemic B cells of chronic lymphocytic leukemia patients despite the presence of Ia antigens.

The human Ia-like antigens, selectively expressed on B lymphocytes, are now recognized to be closely associated with, or identical to, the gene products of the major histocompatibility complex responsible for stimulation in the mixed lymphocyte reaction. The leukemic B lymphocytes of patients with chronic lymphocytic leukemia express these antigens very well. In the present study they were readily detected by several techniques utilizing both allo- and heteroantisera. However, the leukemic B cells from most patients were found to be extremely poor stimulating cells in the mixed lymphocyte reaction. This was particularly apparent when comparisons were made on a B-cell basis with isolated normal B lymphocytes. Leukemic cell death, abnormal kinetics of leukemic cell-mediated stimulation, and serum or cellular suppressor factors do not appear to explain these findings. Studies comparing cells from a leukemic patient with those of her HLA identical sibling and results of mixed lymphocyte reactions between normal and leukemic subjects discordant for D-region-associated Ia antigens ruled out genetic explanations for the differences observed. Experiments with normal peripheral blood mononuclear cells depleted of T cells and monocytes exclude the quantitative deficiency of monocytes which is found in the peripheral blood of most leukemic patients as an explanation. The present results with chronic lymphocytic leukemia cells indicate that the mere expression of the Ia-like antigens by cell populations does not render them effective stimulators. The accumulated evidence obtained indicate that abnormalities, particularly of membrane function and metabolism, known to occur in chronic lymphocytic leukemia lymphocytes may be involved in the poor stimulatory capacity of the leukemic B cells.

Animals↗
PubMed1979

T cell helper defect in patients with chronic lymphocytic leukemia.

Purified peripheral blood T lymphocytes from normal donors were shown to help allogeneic tonsillar B cells to differentiate and secrete specific anti-SRBC antibody in vitro in a plaque-forming assay. Utilizing this system, a comparison was made between the allogeneic helper activity generated by the T cells of normal individuals and patients with various disease states. Allogeneic helper activity was absent when T lymphocytes from patients with CLL were used. Conversely, relatively normal allogeneic helper function was provided by T cells of patients with a variety of other disorders studied. Thus, a functional deficiency was identified in CLL patients in the subpopulation of regulatory T cells responsible for providing helper activity in allogeneic interactions.

B-Lymphocytes↗
PubMed1978

Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes.

Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.

B-Lymphocytes↗
PubMed1978

Ia-bearing T lymphocytes in man. Their identification and role in the generation of allogeneic helper activity.

The presence of Ia-like antigens was demonstrated on a small population (2-6%) of highly purified human circulating T lymphocytes by immunofluorescence with a rabbit anti-Ia serum raised against the isolated bimolecular Ia structure. The Ia+ T lymphocytes have no surface or intracellular immunoglobulins. The expansion of this Ia+ T-cell population was encountered in certain patients. Ia antigens were also found on T blasts grown in long-term cultures with conditioned medium generated by phytohemagglutinin-stimulated lymphocytes. In addition, leukemia blasts which stained for Ia antigens and formed E rosettes were identified in the peripheral blood of two leukemic patients. This evidence further supports the existence of Ia-bearing T cells in man. The Ia+ T-lymphocyte population was shown to contain cells responsible for the generation of allogeneic helper activity. Elimination of Ia+ lymphocytes from a purified T-cell population by the anti-Ia antiserum and complement abolished its ability to help an allogeneic B-cell preparation to generate plaque-forming cells against sheep erythrocytes in vitro in the presence of the antigen.

Antigens, Surface↗
PubMed1978

Lymphoblastoid cell lines from patients with chronic lymphocytic leukemia: identification of tumor origin by idiotypic analysis.

Multiple lymphoblastoid cell lines have been derived from two patients with chronic lymphocytic leukemia with an associated monoclonal immunoglobulin (Ig) band. Idiotypic antisera raised against the monoclonal serum Ig bands were shown to be specific for the membrane Ig of the patients' leukemic cells. The idiotypic determinants in these patients thereby constitute tumor-specific antigens. Surface and intracellular immunofluorescence studies utilizing these idiotypic antisera were used to identify the cell lines of leukemic origin. These studies showed that certain cell lines from each patient were derived from the leukemic cells while other cell lines were derived from residual normal B lymphocytes. The leukemic cell lines were variable and contained different percentages of lymphoid cells with the idiotype-specific membrane Ig and, in addition, different percentages of plasma cells with intracellular Ig of the same specificity. Specific Ig synthesis was also demonstrated by hemagglutination-inhibition analysis of cell line supernatants. Aside from Ig specificity, no differences have been found between the leukemic cell lines and those derived from normal cells. One of the leukemic cell lines was cloned in soft agarose. All the clones were shown to be of leukemic origin.

Aged↗
PubMed1978

Patterns of expression of human "Ia-like" antigens during the terminal stages of B cell development.

The "Ia-like" antigens characteristically present on the membrane of B lymphocytes were shown to be absent in most terminally differentiated Ig-producing plasma cells. This was most evident in analyses of myeloma plasma cells that uniformly lacked the Ia-antigens. Also, in B lymphoid cell lines, the lymphoblasts were uniformly Ia-positive but the plasma cells were negative. In contrast, however, the majority of plasma cells produced after pokeweed mitogen stimulation remained positive. Plasma cells in tonsil and in the tissue of peripheral blood of patients with Wladenström's macroglobulinemia were also sometimes Ia-positive although the majority were negative. Studies of membrane IgM and IgD indicated a similar loss in some instances. However, the SIg and Ia antigens were not invariably associated. These results lead to the conclusion that Ia-antigens are differentiation antigens for B cells and are usually lost by the end stage cells in this series.

B-Lymphocytes↗
PubMed1977

An unusual kappa immunoglobulin antigen present on the membrane of T and B lymphocytes.

Several K immunoglobulin antisera out of a large number studied showed the unique property of reacting with a membrane structure present on all T and B lymphocytes examined. This antigen was detected on lymphocytes by indirect fluorescence, direct fluorescence, and by cytotoxic analysis. Absorption of the antiserum by all K myeloma proteins, K Bence-Jones proteins, and kappa light chains removed the activity; L proteins had no effect. The possibility that the cross-reacting membrane antigen is part of the HL-A system was discussed.

Antibody Specificity↗
PubMed1977

Receptors for IgM on certain human B lymphocytes.

A receptor for IgM was demonstrated on the surface of human B lymphocytes by using a rosette technique with ox erythrocytes coated with rabbit IgM antibody (EAM). Lymphocytes forming rosettes with EAM did not bind sheep red cells, had membrane Ia-like antigens and, in some instances, surface immunoglobulin. The specificity of EAM rosettes was confirmed by inhibition experiments with purified human Ig. IgM but not IgG molecules inhibited the rosette reaction. In addition, inhibition of EAM rosettes with IgM fragments showed that the receptor has affinity for a part of the molecule located in the Fc portion. By analogy with the receptors previously found on certain human T cells, receptors for IgM were not detected on freshly isolated B cells, but were expressed after overnight culture in IgM-free media. Studies on different human lymphoid tissues showed that IgM receptors are expressed on a limited percentage of both circulating and noncirculating B cells. In addition to normal B cells, the malignant B cells of a majority of cases of chronic lymphocytic leukemia expressed the receptors for IgM.

Animals↗
PubMed1976

Lymphocyte surface membrane immunoglobulin.

Demonstration of surface Ig on lympohcytes is subject to interference by the formation of immune complexes between the fluorochrome tagged antibodies and minute amounts of residual serum Ig present in the fluid phase or loosely bound to the Fc receptor. These newly formed immune complexes accordingly bind to Fc receptors, including those of the Fc-positive Ig-negative third population, and result in falsely elevated percentages of Ig-bearing cells. In principle, this immune complex formation can occur with any soluble antigens, but in practice it is most commonly encountered with IgG and to a lesser extent with IgM or IgA determinations. The use of fluorochrome tagged F(ab')2 fragments of antibodies in fluorescence results in an immune complex without an exposed Fc region that does not bind to Fc receptors. Methods for preparation of the F(ab')2 fragments are described. The use of latex ingestion as an aid for the identification of monocytes has the additional effect of allowing autoreactive anti-lymphocyte antibodies to elute from the cell surface and thereby diminishes this additional source of false positive surface fluorescence.

Antigen-Antibody Complex↗
PubMed1975

The occurrence of the HL-B alloantigens on the cells of unclassified acute lymphoblastic leukemias.

Six cases of acute lymphoblastic leukemia were studied by a variety of T- and B-lymphocyte surface markers. Two appeared to represent T-cell leukemias with the lymphoblasts forming sheep erythrocyte rosettes. The other four lacked all the usual membrane markers. However, indirect immunofluorescence with alloantisera detected the presence of the Ia-related HL-B antigens on the cells of the latter four cases; these antigens were absent in the first two cases. The primary association of the HL-B antigens with B cells raises the possibility that the positive group of cases are of B-cell lineage.

B-Lymphocytes↗
PubMed1975

Mixed lymphocyte culture determinants and C2 deficiency: LD-7a associated with C2 deficiency in four families.

Four families with C2 deficiency were studied. Among eight HL-A haplotypes involved with C2 deficiency, five were HL-A 10,W18. Three homozygotes for C2 deficiency from different families were mutually nonreactive in mixed lymphocyte cultures (MLC) and the heterozygotes from the fourth family failed to react to the homozygous cells. It appeared that identical MLC determinants were associated with all the genes from the different families that related to C2 deficiency. Further experiments identified the MLC determinant, LD-7a, as being involved. These results suggest marked linkage disequilibrium between the genes for C2 deficiency and the major histocompatibility complex (MHC). Studies of possible recombinants have offered tentative evidence for the positioning of the locus for C2 deficiency with respect to other segments of the MHC.

Chromosome Mapping↗
PubMed1975

Recognition by pregnancy serums of non-HL-A alloantigens selectively expressed on B lymphocytes.

A group of alloantibodies are found in pregnancy sera which react with antigens present on B lymphocytes and monocytes but are not detectable on the vast majority of unstimulated T cells. This specificity distinguishes them from HL-A antibodies which react with both cell types. They were readily recognized through indirect fluorescent antibody analysis by employing the combination of B-cell lymphoid lines and normal peripheral blood T cells. Different sera gave a variety of patterns of reactivity with a panel of 11 lymphoid lines. Similar differential patterns were also observed with normal B cells from different individuals particularly after concentrating the B cells. The antibodies were also cytotoxic to B cells and this procedure gave parallel results to the fluorescence method. The pattern of reactions obtained indicated a very heterogeneous system similar to that for HL-A. Special study of certain of the sera provided evidence that the lymphocyte-defined determinants of the mixed lymphocyte reaction system were involved. For convenience the term HL-B has been employed for these antigens.

Antibody Specificity↗