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Biomedical subjects

R Billing

Publications and source records attributed to R Billing.

At least 37 records · Page 2Linked to original sources

Selective reactivity of sera from alloimmunized sheep and cattle against human T and leukemia cells.

Human B and T lymphocytes from a panel of healthy individuals were tested against serial dilutions of 68 mare, 81 cow, 7 sow, and 87 ewe sera. All the animals had been alloimmunized by pregnancies and/or blood transfusions. Weak correlations with HLA-A, B, C, and DR specificities were found in 20 sera. Twelve other sera, 9 from ewes and 3 from cows, had a strong reactivity against T lymphocytes but weak or no reactivity against B cells, spleen null cells, granulocytes, and platelets, suggesting a non-major histocompatibility complex (MHC) cross-reactivity. They were cytotoxic for most of the cells of malignant proliferative origin tested thus far, including T acute lymphoblastic leukemia (T ALL), common ALL (cALL), acute myeloblastic leukemia (AML), and Sezary cells, but were negative with B lymphoblastoid cell lines and cells from patients with B chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML). The hypothesis that humans and certain other mammals share a common determinant on T-lineage cells and some malignant cells is advanced.

Animals↗

Monoclonal and heteroantibody reacting with different antigens common to human blast cells and monocytes.

A mouse monoclonal antibody CBL1 and a rabbit heteroantisera 157 raised to a lymphoblastoid T ALL cell line, CEM, appear to be specific for blast cells. Both CBL1 and 157 reacted with all PHA blasts and lymphoblastoid cell lines and the majority of leukemic blast cells tested. From serological reactivity and immunoprecipation experiments, CBL1 and 157 appeared to detect different blast cell antigens. There were leukemia blast cells from six patients that gave a different reaction pattern with CBL1 and 157. Antiserum 157 immunoprecipitated a 90,000 dalton antigen under reducing conditions which appeared as a 180,000 dalton disulfide-linked dimer under nonreducing conditions. Immunoprecipitation with CBL1 using the same 125I-labeled cell lysates gave no observable antigenic peaks.

Antibodies↗

Treatment with anti-Ia and antiblast/monocyte monoclonal antibodies can prolong skin allograft survival in nonhuman primates.

Two monoclonal antibodies, one directed against human Ia antigens and the other reactive to both monocytes and blast cells, were evaluated for prolonging skin graft survival in Rhesus monkeys. Various doses of the antibodies were given intravenously until the skin graft was rejected. Compared with a graft survival of five days for untreated control monkeys, five animals receiving anti-Ia had grafts surviving from 13 to 19 days and six animals treated with antiblast/monocyte antibody had grafts surviving from 15 to 22 days. No adverse side effects were seen with treatment with antiblast/monocyte antibodies. However, the dose of anti-Ia antibody was critical in that four monkeys died of anaphylaxis when injected with amounts exceeding 200 microliters of ascites with a titer of 1:10(5).

Animals↗

A monoclonal antibody recognizing a determinant common to HLA-A3 and A11.

Spleen cells from a mouse immunized with an AML cell expressing HLA-A3 produced a hybridoma secreting an anti-HLA-A3, A11 monoclonal antibody, 26D3. By complement-dependent cytotoxicity at dilutions to 1:10(4) the ascites antibody lysed 13/13 A3, 15/15 A11, and 8 other lymphocytes from a panel of 98 donors. The 26 D3 immunoprecipitated a molecule consisting of subunits of 44,000 and 12,000 daltons. Monoclonality of the antibody was demonstrated by isoelectric focusing and protein A affinity chromatography.

Animals↗

A new acute leukemia-associated blast cell antigen detected by a monoclonal antibody.

A monoclonal mouse antibody has been raised to the common acute lymphoblastic leukemia (cALL) cell line Reh. It is a cytotoxic antibody of the IgG2, subclass that reacts with leukemia cells from the following patients: 69% non-B non-T ALL, 50% T-ALL, 18% acute myeloblastic leukemia (AML), and 66% chronic myeloid leukemia (CML) blast crisis lymphoid cells. Other types of leukemia and all normal blood cells tested were negative, including T and B lymphocytes, granulocytes, monocytes, erythrocytes, and spleen cells. The detected antigen appears to be a type of blast cell antigen because it is also present on phytohemagglutinin (PHA) blast cells, myeloblast from normal bone marrow cells (by CFU-C), and all lymphoblastoid cell lines tested. Only one active antibody species could be detected by preparative isoelectric focusing on polyacrylamide gels and by protein-A-Sepharose affinity chromatography.

Acute Disease↗

Cytotoxic monoclonal antibody to a human leiomyosacoma.

A monoclonal antibody produced by the hybridoma technique against a human leiomyosarcoma was highly cytotoxic in dilutions of 1:64 000 to the original tumour cells. The antibody was unreactive with most normal cells (lymphocytes, 120 donors; spleen cells, 73/75; monocytes, 16; granulocytes, 25; platelets, 12; red cells, 11) and could not be absorbed out by smooth muscle from the small intestine or by spleen cells. Its specificity for the tumour was high since it did not react with cells from 40 patients with leukaemia, from 8 patients with other tumours, and from 7 cultured tumour lines. The only other cell that it reacted with (at 1:4000 dilution) was line 8402, a T acute lymphocytic leukaemia line. This monoclonal antibody may be suitable for therapeutic trials.

Antibodies, Neoplasm↗

Detection of differentiation antigens by use of monoclonal antibodies.

Various monoclonal antisera placed at appropriate dilutions in a microcytotoxicity typing tray can be used to characterize different cell types with the aid of a simple 2-h microcytotoxicity test. With this simple assay, T and B lymphocytes, granulocytes, monocytes, blast cells, and platelets can readily be distinguished. In addition, spleen cells contained 25-50% T cells, half of which expressed Ia antigens. The presence of Ia-bearing T cells in peripheral blood lymphocytes of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients can also be detected using this cytotoxicity tray.

Antibodies, Monoclonal↗

Somatic cell hybrid analyses of hematopoietic differentiation.

A differentiated cell expresses an entire set of specialized features. Somatic cell hybridization provides a method to examine control of gene regulation. We studied the expression of tissue-specific features in hybrids between human promyelocytes (HL-60) and human Burkitt's lymphoma cells (P3HR-1). Two hybrid lines, HP-1 and HP-2, and 18 hybrid clones were established and confirmed by karyotype, isozyme, and surface antigen analyses. The hybrids extinguished the 10 myeloid (HL-60) features that we examined including myeloid morphology, histochemistry, and functions that included response to colony-stimulating factor and ability to differentiate to granulocytes or macrophages. In contrast, the hybrids synthesized immunoglobulin and expressed Epstein-Barr nuclear, early, and viral capsid antigens similar to the P3HR-1 lymphoid parental line. Results are contrasted to the findings when P3HR-1 lymphocytes are fused to human erythroid-myeloid cells (K562). Taken together, our results suggest that phenotypic differences between human myeloid and lymphoid cells in the hematopoietic lineage involve mutually exclusive programs and may possibly be mediated by the activity of diffusible, transacting molecules.

Antigens, Viral↗

Functional properties of subsets of T lymphocytes defined by specific antigens.

Heteroantisera raised to the acute lymphocytic T (ALL) cell line HSB2 and to Sézary cells react with distinct subpopulations of T lymphocytes. Each antiserum reacts with a different T cell antigen and defines a distinct subpopulation that represents approximately 50% of peripheral blood T lymphocytes. The anti-HSB2-positive subpopulation contained suppressor cells for pokeweed mitogen-dependent immunoglobin (Ig) synthesis whereas the anti-Sézary cell serum-positive population included helper cells for Ig synthesis and mixed lymphocyte responder cells.

Antigens↗

Human alveolar macrophages express Ia-like antigens.

Monoclonal antibody to la-like antigens was used to demonstrate the presence of these antigens on human alveolar macrophages. Immunoprecipitation demonstrated the 27,000 and 34,000 molecular weight peaks that correspond to the la-like antigen subunits. Immunofluorescence confirmed the presence of la-like antigens on alveolar macrophages but not on other bronchoalveolar cells. The presence of alveolar macrophage la-like antigens may be important in cellular interactions.

Antibodies, Monoclonal↗

Preliminary evidence of dual-marked lymphocytes in thoracic duct lymph fluid.

Thoracic duct lymphocytes from patients receiving thoracic duct drainage as a pretransplant therapy were examined for cell surface markers. Patients followed over the drainage time period showed a variable but decreasing percentage of E-rosette-positive cells in the lymph fluid. A substantial percentage of these E-rosette-positive cells also had C3 receptors on their cell surface. Reactions of the whole lymphocytes with a heteroantisera to human B-lymphocyte antigens reflected the increasing proportion of B cells in the samples, but also indicated that a fraction of the T cells have Ia-like antigens on their surface marker characteristics. Significance of these cells with respect to graft survival is discussed.

Animals↗

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1).

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.

Cell Line↗

Requirement for B-lymphocyte alloantigen in the production of neutrophil migration inhibition factor from T lymphocytes (NIF-T).

Neutrophil migration inhibition factor from T lymphocytes (NIF-T) is produced in response to mitogens as the result of cellular interactions between T and B lymphocytes. The requirement for B-cell alloantigen in this interaction process was indicated by (1) collaboration between peripheral blood T cells with various B lymphoblast cell lines but not with non-B lymphoblast cells for NIF-T production, (2) inhibition of NIF-T production by treating collaborating B lymphoblasts with B-cell specific antiserum, and (3) inhibition of NIF-T production by peripheral blood lypmphocytes in the presence of anti-B-cell antiserum and F(ab')2 with anti-B-cell specificity.

Antibody Specificity↗