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Biomedical subjects

M D Cooper

Publications and source records attributed to M D Cooper.

At least 307 records · Page 17Linked to original sources
PubMed1982

Human B cell differentiation. II. Pokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation.

Surface immunoglobulin D (IgD)-positive lymphocytes precoated with monoclonal anti-delta antibody were selectively removed from blood mononuclear cell preparations by "panning" and by fluorescence-activated cell sorter. The depletion of sIgD+ cells did not significantly affect plasma cell responses to pokeweed mitogen PWM). PWM-responsive B cells lacking sIgD and mouse erythrocyte receptors preferentially sedimented in lower density fractions of a discontinuous Percoll gradient, and sIgD-negative B cells were found to have a larger mean diameter than IgD-positive cells. We conclude that PWM-responsive B cells represent a distinct subpopulation of relatively large cells that have ceased to express receptors for mouse erythrocytes and surface IgD.

Animals↗
PubMed1982

Human b-cell differentiation. I. Analysis of immunoglobulin heavy chain switching using monoclonal anti-immunoglobulin M, G, and A antibodies and pokeweed mitogen-induced plasma cell differentiation.

Monoclonal antibodies were used to examine the immunoglobulin isotypes expressed by B lymphocyte precursors of IgM, IgG, IgA, and IgA2 plasma cells. Plasma-cell differentiation was induced by the addition of pokeweed mitogen to cultures of blood mononuclear cells. Anti-mu, -gamma, -alpha, and -alpha 1 antibodies were used in some experiments to inhibit differentiation of B lymphocytes bearing these heavy chain isotypes, and for selective removal of B lymphocyte precursors before culture with pokeweed mitogen in other experiments. Three major subpopulations of B lymphocyte precursors were identified: (a) a subpopulation of surface (s) IgM+ precursors of IgM plasma cells that did not express IgG or IgA isotypes, (b) a subpopulation of sIgG+ precursors of IgG plasma cells of which approximately one-half bore some IgM and none had detectable IgA receptors, and (c) a subpopulation of sIgA+ precursors of IgA plasma cells; one half of these precursors could be shown to express functional IgM receptors but none were found to express IgG receptors. The sIgA subpopulation could be further subdivided into sIgA1+ precursors of IgA1 plasma cells and IgA1-negative precursors of IgA2 plasma cells. These results suggest that normal human B cells can switch from mu directly to each of the other heavy chain isotypes, and that these represent the main switch pathways.

Animals↗
PubMed1982

Postnatal expansion of the natural killer and keller cell population in humans identified by the monoclonal HNK-1 antibody.

Human natural killer (NK) and killer (K) cells were directly enumerated using a monoclonal antibody (HNK-1) and an immunofluorescence assay. The frequency of cells bearing surface HNK-1 antigen was very low in the newborn (less than 1.0%) and increased progressively through childhood and into adult life. This was correlated with an age-related increase in functional NK and K cell activities. Males had a slightly higher proportion of HNK-1+ cells than females. In addition to HNK-1 expression on the surface membrane, a prominent cytoplasmic expression of HNK-1 antigen was found in some but not all surface HNK-1+ cells. The cytoplasmic accumulation of HNK-1 molecules appeared to occur in more mature cells of this lineage.

Adolescent↗
PubMed1982

A subpopulation of small pre-B cells in rabbit bone marrow expresses kappa light chains and exhibits allelic exclusion of b locus allotypes.

The expression of immunoglobulin heavy and light chains by pre-B cells and B lymphocytes was examined by two-color immunoflourescence in heterozygous b5b9 rabbits. Allelic exclusion of b5 and b9 kappa light chain allotypes was observed for both surface immunoglobulin-negative pre-B cells and surface immunoglobulin-positive B lymphocytes. In newborn bone marrow, pre-B cells and immature B lymphocytes expressing b9 were as numerous as those expressing b5. In contrast, circulating B cells and bone marrow plasma cells expressing the b5 marker outnumber b9+ cells by 2 to 1 in adult b5b9 animals. Whereas most B lymphocytes expressed kappa light chain b allotypes, approximately 80% of the micro heavy chain-positive pre-B cells did not. The pre-B cells that expressed detectable light chains were relatively small lymphocytes. A model is presented which includes a "transitional" pre-B cell that expresses both micro chains and kappa chains.

Alleles↗
PubMed1982

Immunoglobulin isotype expression of normal pre-B cells as determined by immunofluorescence.

We have undertaken an immunofluorescent analysis of the immunoglobulin heavy and light chains expressed by pre-B cells from normal human fetal and adult bone marrow using purified mouse monoclonal and goat antibodies to human immunoglobulin isotypes. Our results indicate that (i) the great majority of normal pre-B cells in both fetuses and adults expresses intracytoplasmic mu chains only, (ii) immunoglobulin light-chain synthesis may be initiated during a late stage in pre-B-cell development, and (iii) heavy-chain isotype switching at the pre-B-cell stage may not occur during normal B-cell development.

Adult↗
PubMed1982

In vitro kinetics of phagocytosis and intracellular killing of gonococci by peritoneal macrophages from mice deficient in complement component 5.

Unstimulated resident peritoneal macrophages were harvested from complement-sufficient (C5+) and complement-deficient (C5-) mice by peritoneal lavage and cultured for 14 h. Adherence to cover slips was determined, and the monolayer was infected with transparent T1 gonococci. At various times after infection, the macrophages were observed for both attachment and phagocytosis of the gonococci by scanning and transmission electron microscopy. this analysis indicated that C5+ macrophages were capable of immediate phagocytosis of gonococci, with maximal phagocytosis occurring by 60 to 90 min. In contrast, C5- macrophages had a greater lag time before initiation of phagocytosis; this event was started by 30 min and completed by 90 min. The intracellular gonococci which were phagocytized by either C5+ or C5- mice were completely killed after 30 min of incubation. It appears that C5- mice are at a disadvantage in the early kinetics of the phagocytosis of gonococci, but that this does not affect the ultimate intracellular destruction of gonococci.

Adhesiveness↗
PubMed1982

Characterization of the immune response in subcutaneous chambers of guinea pigs immunized with a ribosomal preparation from Neisseria gonorrhoeae.

Immunization of guinea pigs with ribosomal preparations has been previously shown to be protective against chamber infection with Neisseria gonorrhoeae, and this protection could be correlated with the presence of serum bactericidal antibody. Analysis of the chamber fluids from ribosome-immunized and nonimmunized guinea pigs has demonstrated that the chamber fluid may accurately reflect serum antibody levels and proteins. At least one major population of antiribosomal antibodies is present in both immune serum and chamber fluid as revealed by lines of identity between these components. Antibody- and complement-mediated bactericidal assays revealed that matched chamber fluids and sera from immune animals had comparable bactericidal titers. These results suggest that the antibody-complement-mediated bactericidal activity plays a major role in the protection against N. gonorrhoeae infection. Protection could not be explained on the basis of the cellular components of the inflammatory response since both immune and nonimmune chambers had comparable increases in polymorphonuclear neutrophils, monocytes, and lymphocytes after challenge.

Animals↗
PubMed1982

Natural killer (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology.

Children with the Chediak-Higashi (CH) syndrome are known to have abnormalities of natural killer (NK) cell function. We used the HNK-1 monoclonal antibody that reacts specifically with human NK and K cells to distinguish whether this abnormality was due either to a numerical deficiency of NK cells or a defect in their ability to function. In eight CH patients, a significant proportion of their blood mononuclear cells (10--19%) expressed the HNK-1 differentiation antigen. The level of NK cells in the five children with CH syndrome was higher than for age-matched normal controls (15.8% vs. 5.8%, P less than 0.001). When HNK-1+ cells were isolated with a fluorescence-activated cell sorter, the NK cells from CH patients were a homogeneous population of lymphocytes with a single large granule rather than the multiple small granules seen in Nk cells from normal individuals. The purified HNK-1+ cells from the CH patients had minimal NK or K cell function. The CH syndrome thus includes a functionally defective population of NK cells that retain the capability of expressing the HNK-1 differentiation antigen.

Adolescent↗
PubMed1982

Evidence for an IgD homologue on chicken lymphocytes.

Chicken lymphocyte membrane immunoglobulins (Ig), were precipitated with mouse monoclonal antibodies specific for heavy and light chain isotypes and analyzed by polyacrylamide gel electrophoresis. Very little or no membrane-bound IgG and IgA was detected. After sequential precipitation and removal of IgM reactive with any of three monoclonal anti-mu antibodies, anti-light chain antibody precipitated residual Ig with a relative electrophoretic mobility similar to that of IgM. Under reducing conditions, these surface Ig molecules had a heavy chain that appeared slightly larger (approximately 81,000 daltons) than mu-chain (approximately 79,000 daltons), and light chains of approximately 25,000 daltons. Complete clearance of membrane-bound IgM reactive with an anti-mu allotype antiserum left similar molecules precipitate by monoclonal anti-light chain antibody. These non-IgM molecules could be detected on the surface of lymphocytes from blood, spleen, bursa and the B cell line RAV-1, but not from thymus or blood from an agammaglobulinemic chicken. After capping of B cell surface IgM with anti-mu, immunofluorescent staining with anti-light chain antibody revealed residual Ig molecules disturbed across the surface of more than 90% of the IgM-bearing cells. The data suggest the existence of an avian homologue of mammalian IgD. Affinity-purified goat anti-mu antibodies and a fourth monoclonal anti-mu antibody reacted with both IgM and the putative IgD molecules, which suggests that the IgD homologue shares at least one common determinant with chicken IgM.

Animals↗
PubMed1982

Microenvironmental studies of pre-B and B cell development in human and mouse fetuses.

Immunofluorescence techniques were used to trace the development of cells expressing mu heavy chains in humans and mice. IgM B cells were distinguished from pre-B cells by their additional expression of kappa or lambda light chains. Generation of pre-B and progeny B cells was evident in hemopoietic fetal liver and bone marrow, but not in thymus, heart, lung, spleen, kidney, and placental tissues. Pre-B and B cells, in a ratio of 2 to 1, were abundant in sections of hemopoietic liver and in bone marrow from 12- to 15-wk-old human fetuses, whereas these cells were rare in nonhemopoietic liver samples obtained beyond the 34th week. In mouse fetal liver mu+ cells appeared first around the 12th day of gestation and increased in frequency throughout the third trimester. On day 17 of gestation, kappa light chain expression by 1% of mu+ cells was noted, and the percentage of kappa+/mu+ cells increased progressively to more than 80% by 5 days after birth. Pre-B and B cells were interspersed among myeloid and more abundant erythropoietic cellular elements in the extrasinusoidal areas adjacent to hepatic cords. A loose clustering or "starburst" distribution pattern of pre-B cells became evident around day 17. These observations suggest a model for in situ generation of pre-B and progeny B cells in the hemopoietic fetal liver. In the midst of more numerous erythropoietic elements, immunoglobulin-negative precursors divide to generate a loose colony of mu+ pre-B cells that divide again before giving rise to a wave of IgM B cells.

Animals↗
PubMed1982

Human blood monocytes and platelets share a cell surface component.

We describe a surface determinant shared by human monocytes and cells of the megakaryocytic axis that has been identified using a mouse monoclonal antibody. This monocyte-platelet antigen (MPA) is expressed on all (greater than 99%) of peripheral blood monocytes, platelets, and megakaryocytes. It is also expressed weakly on the monocytic cell line U937 and the promyelocytic line HL60 and is present on cells from 3 of 4 AML patients examined. It is absent from polymorphonuclear leukocytes, T and B lymphocytes, erythrocytes, and a panel of hematopoietic cell lines. MPA is stripped from monocyte membranes with pronase and is reexpressed overnight. The determinant is carried on a noncovalently linked biomolecular complex with molecular weights of 93,000 and 135,000.

Animals↗
PubMed1982

Mouse monoclonal antibodies to chicken VH idiotypic determinants reactivity with B and T cells.

We have prepared mouse monoclonal antibodies against idiotypic (Id) determinants on chicken antibodies to N-acetylglucosamine (NAGA) and p-aminobenzoic acid (PABA) made by inbred line EL 6(3) birds. The monoclonal anti-NAGA Id antibody, termed CId-1, reacted with affinity purified antibodies to NAGA, but not with antibodies specific for PABA, arsanilic acid (Ars), phosphorylcholine (PC), or with normal chicken IgG and IgM. The monoclonal anti-PABA ID antibody, termed CId-2, reacted with anti-PABA antibodies and to a lesser extent with anti-Ars antibodies, but not with anti-NAGA, anti-PC, and normal IgG and IgM. The Id determinants were found among antibodies to NAGA and PABA made by outbred and inbred lines of White Leghorn chickens. The binding of the CId-1 and CId-2 antibodies to intact homologous anti-NAGA and anti-PABA antibodies, respectively, was not hapten-inhibitable in either case. Both anti-Id antibodies reacted specifically with isolated homologous heavy chains, suggesting VH Id specificities. The monoclonal CId-1 and CId-2 antibodies were reactive by immunofluorescence with approximately 0.9 and 0.2%, respectively, of the circulating lymphocytes and with approximately 0.4 and 0.15 of plasma cells. CId-1+ and CId-2+ bursal cells were first detected on the 16th and 14th days of incubation, respectively; both reached maximal frequencies by the 17th day of incubation. The CId-2 antibody reacted exclusively with immunoglobulin-positive cells. The CId-1 antibody also reacted with a subpopulation (0.4%) of immunoglobulin-negative lymphocytes from normal and agammaglobulinemic chickens, and thus would appear to recognize an idiotypic determinant expressed by certain clones of B and T cells.

4-Aminobenzoic Acid↗
PubMed1982

Studies on the clonal origin of human B cell leukemia using monoclonal anti-idiotype antibodies.

The clonal origin of an IgA1 kappa B cell leukemia in a 71-year-old man (WF) was examined using a monoclonal anti-Id antibody and a panel of monoclonal anti-VH antibodies. Immunofluorescent studies revealed that all surface IgA1 kappa + leukemic cells in WF's blood and 10% of the IgM+ B cells in his bone marrow expressed the WF Id. Three percent of the IgA1 kappa + leukemic cells in blood also expressed gamma-chains in their cytoplasm. Approximately 0.1%, 1%, and 10% of bone marrow mononuclear cells, respectively, expressed mu-chains, gamma-chains, and alpha-chains in their cytoplasm, but no detectable light chains or surface immunoglobulins. These mu, gamma, and alpha-positive cells had the convoluted nucleus and narrow cytoplasm characteristic of normal mu+ pre-B cells. Sequential isotype switching among this unusual pre-B population was indicated by co-expression of mu-chains and alpha-chains by 11% and 63%, respectively, of the gamma pre-B cells. These pre-B cells and the surface alpha-chains and cytoplasmic gamma-chains of the leukemic B cells were reactive with one of four monoclonal anti-VH antibodies. The data suggest malignant transformation of the clone before isotype switching, and also imply light chain precommitment at the pre-B cell level of differentiation.

Aged↗
PubMed1982

Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability.

Human lymphocytes with NK and K cell activities can be identified by the HNK-1 (Leu-7) monoclonal antibody. In these experiments, subsets of HNK-1+ cells from blood and bone marrow were distinguished by their expression of other cell surface antigens, their morphology, and their NK functional capability. Two-color immunofluorescence analysis revealed that subpopulations of HNK-1+ cells in blood expressed antigens found on mature T cells (e.g., T1, T3, T4, T8), but none expressed antigens characteristic of immature T cells (T6, T9). The majority of HNK-1+ cells (greater than 60%) also expressed a myeloid antigen (M1), whereas a minority (less than 25%) expressed HLA-DR. HNK-1+ cells were separated into T3- and T3+ subsets with the fluorescence-activated cell sorter and analyzed for their morphology and NK cell function. HNK+T3- cells exhibited a high level of NK activity against K562 target cells and contained many cytoplasmic granules. On the other hand, HNK+T3+ cells had low NK activity and a paucity of cytoplasmic granules. The cell sizes of HNK+T3- and HNK+T3+ cells were indistinguishable by light-scatter analysis. When these cell fractions were analyzed further, a reciprocal relationship between T3 and M1 antigen expression was observed. These results thus delineate two distinct subsets of human HNK-1+ cells in blood with different cytotoxic capability: HNK+T3-M1+ and HNK+T3+M1- cells. Analysis of bone marrow cells demonstrated that only 0.7% of the nucleated cells expressed the HNK-1 antigen; virtually all of these cells expressed both the T3 and T8 antigens but lacked the M1 antigen. Thus, a majority of HNK-1+ cell population in blood were T3-M1+, whereas almost all bone marrow HNK-1+ cells were T3+M1-. We propose that these subsets of cells represent different stages in NK cells differentiation.

Antigens, Surface↗
PubMed1982

Two new acute lymphoblastic leukemia cell lines with early B-cell phenotypes.

Two leukemic cell lines (697 and 207) were established from bone marrow cells obtained from children with ALL in relapse. These cell lines were positive for the common-ALL antigen (CALLA), the HLA-DR (i.e., Ia-like) antigen, and for cytoplasmic and surface IgM heavy chains. The lines were negative for other immunoglobulin heavy chains and light chains. The lines had elevated levels of terminal deoxynucleotidyl transferase enzyme and expressed surface antigens found on normal myeloid-macrophage cells (MMA) and on natural killer cells (HNK-1). A minority of cells in line 207 expressed the T-1, T-6, and Leu-1 antigens as detected by monoclonal antibodies. Line 697 was positive for Epstein-Barr virus (EBV), while line 207 did not possess EBV. Line 697 carried a marker chromosome (identified as a translocation between chromosomes 7 and 19), which was also patient's fresh leukemic cells. The leukemic origin of the cell lines was further indicated by their morphological, cytochemical, and immunologic similarity to the patients' leukemic cells. Phenotypically, both cell lines appear to be arrested in a transitional stage of development between pre-B and B cells and express surface antigens usually found on normal and fresh leukemic cells of non-B-cell lineages.

Antigens, Neoplasm↗
PubMed1982

Human B cell differentiation. III. Enhancing effect of monoclonal anti-immunoglobulin D antibody on pokeweed mitogen-induced plasma cell differentiation.

The effects of monoclonal anti-delta antibodies on pokeweed mitogen (PWM) responses of blood mononuclear cells (MNC) were studied. Treatment with anti-delta antibody enhanced both B cell proliferation and plasma cell differentiation, which are T cell-dependent responses. The anti-delta enhancement of plasma cell differentiation, predominantly of IgM plasma cells, was surprising because PWM-responsive subpopulations of B cells have been shown to lack IgD and their plasma cell differentiation is easily and selectively suppressed by anti-mu, -gamma and -alpha antibodies. Treatment of MNC with monoclonal anti-delta antibody enhanced the number of IgM plasma cells induced by PWM stimulation by approximately threefold. The degree of enhancement was dependent upon the concentration of anti-delta antibody, and the F(ab')2 fragments were effective. Maximal enhancement was obtained either when MNC were preincubated with anti-delta antibody for 1 day before PWM stimulation or when anti-delta antibody was added with PWM at the beginning of 7-day cultures. Anti-delta antibody had little or no effect when added 1 to 3 days after the initiation of PWM stimulated cultures. Anti-delta treatment overnight induced a population of small IgM+IgD+ B cells to enlarge and converted them from poor to good PWM responders. The results are discussed in the context of a model which proposed that differentiation of both immature and preactivated mature IgD- cells can be inhibited by signals generated via surface immunoglobulin cross-linkage, whereas this stimulus enhances differentiation of the intermediate IgD+IgM+ B cells.

Antibodies, Anti-Idiotypic↗