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N Gadol

Publications and source records attributed to N Gadol.

13 recordsLinked to original sources

Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes.

Previous studies have indicated that chronic lymphocytic leukemias (CLL) are characterized by the coexpression of CD5 and B-cell antigens, while hairy cell leukemias (HCL) typically express CD11c+CD5- B-cell immunophenotypes. In this report we describe the features of B-cell leukemias with CD11c+CD5+ immunophenotypes and the identification of novel circulating B-cell subsets defined by the expression of CD20, CD5, and CD11c antigens. Morphologic evaluation of 14CD11c+CD5+ B-cell leukemias showed that they generally had larger cellular diameters (14 to 21 microns) and lower nuclear:cytoplasm ratios than typical small lymphocyte CLL. These cases did not exhibit the well-defined nucleoli characteristic of prolymphocytic leukemia (PLL). The presenting clinical features of CD11c+CD5+ B-cell leukemias were most consistent with CLL or PLL, and none of the evaluated cases had pancytopenia, splenomegaly, and cytoplasmic villi characteristic of HCL. Examination of normal peripheral blood (n = 6) by three-color flow cytometry identified four novel B-cell subsets with the following immunophenotypes (mean percent of total CD20+ B cells +/- SE): CD20+CD5+CD11c+ (8.0 +/- 1.6); CD20+CD5-CD11c+ (12.0 +/- 2.0); CD20+CD5+CD11c- (35.0 +/- 4.9); and CD20+CD5-CD11c- (44.0 +/- 5.0). Our findings suggest that CD11c+CD5+ B-cell leukemias with atypical morphologic features represent forms of CLL or PLL rather than HCL. In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias.

Adult

Antigenic phenotype and functional characterization of human tonsil B cells.

Human tonsil cells were labeled with anti-leu-16, a monoclonal antibody (MoAb) that recognizes the CD20 antigen and that is specific for B cells. Two populations of B cells were identified by flow cytometry on the basis of antigen density. One labeled brightly with anti-Leu-16, and the other labeled at a level comparable to blood B cells. These two populations were characterized with a panel of MoAbs in two- and three-color flow cytometric studies and appeared to correspond to germinal-center and mantle-zone B cells. The pattern of staining of anti-Leu-16 on sections of frozen tonsil supported this characterization. Anti-Leu-16 labeled germinal center cells more intensely than mantle zone cells and stained a few scattered B cells in the interfollicular zone. The ability of each Leu-16+ population to secrete IgG and IgM in response to mitogens was measured in a particle immunofluorescence assay. Dim Leu-16+ B cells (small, resting B cells and a subpopulation of preactivated cells) secreted IgG and IgM in response to pokeweed mitogen (PWM) but only IgG in response to B cell growth factor (BCGF). Bright Leu-16+ B cells (small to large activated cells and possibly memory cells) did not respond to PWM but secreted IgG in response to BCGF. The functional responses of dim Leu-16+ and bright Leu-16+ B cells were consistent with their identification as mantle-zone and germinal-center B cells. Phenotypic identification and functional studies of mantle-zone and germinal-center B cells may help clarify the differentiation pathway within the germinal center.

Antibodies, Monoclonal

Phenotypic and functional characterization of human Leu1 (CD5) B cells.

Leu1 B cells have been observed in high numbers in CLL patients, fetal spleen, and in bone marrow transplant recipients. We studied these cells in normal peripheral blood, spleen, and tonsil. They were phenotypically and functionally similar to conventional B cells. Leu1 B cells in the spleen and blood displayed a mature phenotype similar to the Leu1 B cells in the fetus, some expressing high levels of both sIgM and sIgD, and some expressing high levels of sIgD but little sIgM. Most Leu1 B cells in the tonsil also expressed high levels of both sIgM and sIgD, although some tonsil Leu1 B cells had high levels of sIgM but little sIgD. The significance of the Leu1 B cell is unknown, although it may be involved in the humoral immunoincompetence of the fetus, of CLL patients, and of transplant recipients. In our data there is no evidence to suggest that these cells are activated, immature, or capable of an immunoregulatory function.

Antibodies, Monoclonal

Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies.

Examination of the cell surface phenotype of fetal splenic lymphocytes demonstrated a major, novel subpopulation of B cells that co-express Leu-1 (CD5) in addition to B cell differentiation antigens (Leu-1+ B cells). These cells are similar to some conventional B cells in that they express HLA-DR, Leu-12, and B1, as well as both immunoglobulin (Ig) M and IgD. They comprise 40 to 60% of total splenic B cells in the fetus but are infrequent in fetal liver and adult spleen. Fetal Leu-1+ B cells do not respond to pokeweed mitogen with either proliferation or Ig secretion, and in contrast to the murine counterpart, Ly-1 B cells, they do not constitutively produce Ig. Leu-1+ B cells were incapable of augmenting Ig production of Leu-1- B cells when suboptimal numbers of T cells were present; however, they did require the presence of T cells to secrete antibody. They do not cap either the CD5 protein or surface Ig. These cells are a unique subpopulation of fetal splenic B cells that do not function as conventional B cells. Their role in the humoral immune response is unknown. They may represent the normal stage of B cell development, which is reflected in the phenotype of B cell CLL cells.

Antigens, Differentiation, B-Lymphocyte

Leukocyte migration inhibition in recurrent aphthous ulceration.

Leukocyte inhibitory factor (LIF) production in response to streptococcal antigens and oral mucosa was examined as a possible pathogenic mechanism in recurrent aphthous ulceration (RAU). Mononuclear cells from RAU patients and controls were stimulated with antigens prepared from two species of streptococci and from oral mucosa. Candida albicans and foreskin were tested as control antigens. There were some statistically significant differences in leukocyte migration inhibition between patients and controls with some concentrations of Streptococcus sanguis (ATCC 10556) and C. albicans, and a trend toward low migration indices with oral mucosa. However, the roughly equal numbers of patients and controls responding positively to each antigen and the large background variation suggest a lack of biological significance. LIF production did not increase consistently in the early stages and did not correlate with ulcer development in patients studied sequentially. We conclude that LIF production (at least in response to the antigens tested) plays no pathogenic role in RAU. Our data do not support the hypothesis that a specific cell-mediated sensitivity to streptococcal antigens is involved in RAU.

Adult

Lymphocyte function in recurrent aphthous ulceration.

Lymphocyte blast transformation responses to mitogens and to streptococcal, adenovirus Type 1, and oral mucosal antigens were studied in 32 patients with recurrent aphthous ulceration (RAU) and matched control subjects. RAU patients showed significantly depressed (p less than 0.05) responses to mitogens in comparison with matched controls, but there was no significant difference between patients and controls in response to any of the antigens tested. These results indicate that neither cell-mediated hypersensitivity to streptococcal or viral antigens nor cross-reactivity between oral mucosal and streptococcal antigens are likely to play a role in the pathogenesis of RAU. Rather, the data support the hypothesis of an imbalance or defect in immune cell subpopulations.

Antigens

A new method for separating mononuclear cells from whole blood.

The LeucoPREP tube, a new method for separating mononuclear cells from whole blood, is described. The LeucoPREP tube is a 7-ml glass tube which contains a polyester gel and a solution of a sucrose polymer and sodium diatrizoate (Histopaque, Sigma). Platelets, lymphocytes, and monocytes are separated from granulocytes and erythrocytes based on differences in density. Platelets are then removed from the mononuclear cells by washing. The yield, viability, and percentage of various cell subpopulations obtained from the LeucoPREP tube are equivalent to those obtained from standard Ficoll-based methods. However, the LeucoPREP tube is a faster, less technically demanding method than Ficoll. The major advantages of the LeucoPREP tube are that 1) whole blood is added directly into the tube, unlike Ficoll methods, in which the blood must be diluted and carefully layered; and 2) it requires a very short (10 min) centrifugation time. The LeucoPREP tube should be highly desirable to anyone processing many blood samples, for example, clinical laboratories.

Antibodies, Monoclonal

Inhibition of macrophage migration by normal guinea pig intestinal secretions.

The incubation fluid from 24-hr cultures of normal guinea pig small intestines was found to contain activity capable of inhibiting the migration of normal guinea pig peritoneal macrophages. Each of three different culture fluids showed macrophage inhibitory activity in the 25,000-55,000 mol wt range when subjected to Sephadex G-100 gel filtration. One of these three preparations also contained inhibitory activity in the excluded volume. The low molecular weight activity was nondialyzable and heat stable to 56 degrees for 30 min. It was destroyed by boiling for 1 hr, and its activity was reversed by 10(-4)M epinephrine. Based upon these properties it is suggested that this activity was due to migration inhibitory factor (MIF). The high molecular weight inhibitor was stable to heating and its activity was not reversed by epinephrine. This material was most likely endotoxin. The presence of MIF, which may be associated with T-cell activity in the intestine, suggests that cell-mediated immunity (CMI) could play a role in local protection against gut infections. Furthermore, its presence in normal intestinal secretions suggests that some MIF-producing cells are always being stimulated by normal flora. The question is thus raised whether further specific stimulation of local CMI in the gut could be successful.

Animals

Respiratory tract cell-mediated immunity: comparison of primary and secondary response.

A secondary local and splenic cell-mediated immune response was observed and compared to the primary response. Previous studies have demonstrated cell-mediated immunity (CMI) by lymphocytes from bronchopulmonary washings and have shown that its appearance is to a large extent inedpendent of splenic CMI. This study evaluated the secondary as compared to the primary response, with respect to both cellular and humoral immune responses. Guinea pigs were immunized with influenza virus vaccine either nasally or parenterally, booster immunizations were given by the same route, and animals were killed at various times after immunization or booster. The inhibition of macrophage migration was used to assess CMI. As in previous studies, local application of antigen led to mainly local appearance of CMI, whereas parenteral immunization led to mainly systemic CMI. Both pulmonary and splenic lymphocytes showed an inhibition of macrophage migration that appeared 2 to 3 days sooner after the booster, as compared to the primary immunization. There was no evidence, however, for the earlier production or increased amount of antibody in the bronchial secretions in the boosted animals. The results suggest that pulmonary as well as splenic T lymphocytes exhibit memory, but that pulmonary B lymphocytes do not.

Animals