B-cell malignancies: origin and extent of clonal involvement.
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B-Lymphocytes↗
Biomedical subjects
M D Cooper
Publications and source records attributed to M D Cooper.
Epstein-Barr virus-induced immunoglobulin synthesis by B cells from individuals with late-onset panhypogammaglobulinemia.
Epstein-Barr virus (EBV) transformation was used to examine the differentiation potential of circulating B cells from eight individuals with late-onset panhypogammaglobulinemia. Cytoplasmic and secreted immunoglobulins were evaluated by immunofluorescence and radioimmunoassay. EBV-infected cultures of B cells from patients and healthy controls generated similar numbers of IgM-secreting plasma cells, but relatively few IgG and IgA plasma cells were induced in cultures of patients' B cells. As further evidence of B-cell immaturity, approximately 90% of the IgA B cells in the eight patients coexpressed IgM. Clonal diversity of B cells from hypogammaglobulinemic patients was examined with a panel of mouse monoclonal antibodies directed against idiotypic and VH subgroup determinants. The frequencies of EBV-induced plasma cells exhibiting the different idiotypic and VH determinants were similar for patients and controls. The data suggest the continued generation of clonally diverse B cells that are capable of terminal plasma-cell differentiation when the normal triggering mechanisms are bypassed by EBV. The arrested differentiation at an immature B-cell stage in these hypogammaglobulinemic individuals would appear to reflect a defect in normal B-cell triggering.
Adult↗
Catheter-induced coronary artery spasm: an angiographic manifestation of vasospastic angina?
During a 4-year period, 33 patients with angiographic coronary artery spasm in the absence of significant fixed occlusive disease were reviewed. Sixteen patients had typical variant angina and 17 had catheter-induced spasm. All patients had one or more episodes of rest angina. Left ventriculography demonstrated mitral valve prolapse in 14 patients (42%) and end-systolic cavity obliteration in six (18%). Spasm was demonstrated to occur in the right coronary artery in 26 patients and in the left coronary artery in seven. Two patients had multivessel spasm. Comparing patients with variant angina and catheter-induced spasm demonstrated no significant difference in clinical, ECG, or angiographic parameters. Two patients with catheter-induced spasm had healed myocardial infarctions and both developed spontaneous non catheter-induced spasm in the infarct vessel. The majority of patients responded to long-acting nitrate therapy, though those with catheter-induced spasm tended to have more recurrent chest pain. Six patients were placed on calcium antagonist drugs with marked symptomatic improvement in five. This study suggests that patients with catheter-induced spasm are similar to those with variant angina and its angiographic documentation may be a marker for the identification of patients with vasospastic angina.
Adult↗
Immunologic studies in asymptomatic hemophilia patients. Relationship to acquired immune deficiency syndrome (AIDS).
Asymptomatic hemophilia patients receiving Factor VIII concentrate were found to have normal natural killer (NK) cells and B cells, and an inverted T helper/suppressor ratio due to an increase in cells of T suppressor phenotype. In contrast, a hemophilia patient with acquired immune deficiency syndrome (AIDS) exhibited nonfunctional NK cells, low B cells, and an inverted T helper/suppressor ratio due to very low numbers of T helper cells. Hemophilia patients on cryoprecipitate therapy exhibited normal immune parameters. A high percentage of hemophilia patients on both treatments had antibody to hepatitis B virus. The isolated finding of elevated levels of T suppressor cells in hemophilia patients receiving Factor VIII concentrate has not been recognized as an early indicator of impending AIDS, and longitudinal studies will be required to determine its clinical significance.
Acquired Immunodeficiency Syndrome↗
Hyper IgM immunodeficiency. A primary dysfunction of B lymphocyte isotype switching.
Immunological evaluations (lymphocyte markers, B cell differentiation, T cell function) were performed on peripheral blood mononuclear cells from four individuals with hyper IgM immunodeficiency. Number, proportion, and proliferation of T lymphocytes and T lymphocyte subpopulations were relatively normal in affected individuals. The percentage and number of B cells expressing surface IgM and IgD were either normal or elevated in both blood and lymph nodes. However, surface IgG- and IgA-bearing B lymphocytes were completely absent. In vitro stimulation of blood lymphocytes with both T cell-dependent and T-cell independent polyclonal B cell activators resulted in normal numbers of IgM plasma cells and IgM secretion in cultures, but failed to induce any IgG- or IgA-producing cells. This failure of isotype switching was intrinsic to the B cell population and did not involve aberrant T cell help or suppression. Therefore, individuals with this disorder possess an intrinsic B cell dysfunction that is not related to abnormal T cell regulation.
Adolescent↗
Usage patterns of an online search system.
This article examines the usage patterns of the ELHILL retrieval program of the National Library of Medicine's MEDLARS system. Based on a sample of 6759 searches, the study analyzes the frequency of various commands and command options, classifies messages issued by the system, and investigates searcher error rates. The article concludes with suggestions for improving and redesigning both the program and query language.
MEDLARS↗
IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precommitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help.
The human IgG subclasses expressed by circulating B lymphocytes, tissue plasma cells, and plasma cells generated from B cell precursors in response to the polyclonal mitogens LPS and PWM were examined by immunofluorescence using subclass-specific monoclonal antibodies. The subclass distribution observed for circulating B lymphocytes was IgG2 (48%) greater than IgG1 (40%) greater than IgG3 (8%) greater than IgG4 (1%), while the distribution among IgG plasma cells in bone marrow, blood, spleen, and tonsils was IgG1 (64%) greater than IgG2 (26%) greater than IgG3 (8%) greater than IgG4 (1%). Multiple IgG isotypes were not observed on B cells or in plasma cells. Although IgG plasma cell responses to both LPS and PWM were T cell dependent, the distributions of IgG subclasses elicited were strikingly different. In control and LPS-stimulated cultures of blood mononuclear cells, the induced plasma cells expressed the IgG subclass distribution: IgG2 greater than 80%, IgG1 less than 20%, IgG3 less than 1%, IgG4 less than 1%. In PWM-stimulated cultures, the subclass distribution, IgG1 approximately 65%, IgG2 approximately 25%, IgG3 approximately 7%, IgG4 approximately 1%, was in perfect concordance with the in vivo subclass distribution of IgG plasma cells. Selective inhibition of suppressor T cell activity by x-irradiation and mitomycin C treatment did not alter the IgG subclass distribution pattern induced by LPS and PWM. Monoclonal antibodies were used to deplete selectively the B cell precursors bearing IgG1, IgG2, or IgG3 before PWM stimulation of blood mononuclear cells. In each instance, a reduction was observed only in the subpopulation of plasma cells producing the homologous IgG subclass. The results indicate that T cells can preferentially influence the terminal differentiation of B cells that are precommitted to different IgG subclasses.
Animals↗
Expression of C3b receptors on human be cells and myelomonocytic cells but not natural killer cells.
We have examined natural killer (NK) cells, B cells and myelomonocytic cells at different stages of differentiation for the expression of surface C3b receptors (C3bR). Receptor presence was detected using affinity-purified F(ab')2 anti-C3bR antibodies in indirect immunofluorescence assays. NK cells, identified in fetal and adult tissues by the monoclonal antibody HNK-1, were C3bR- except for infrequent C3bR+ HNK-1+ cells in some blood samples. NK cells were not induced to express C3bR by exposure to interferon, target cells, or phorbol myristate acetate. B cells gradually acquired the ability to express C3bR with maturity: 15% of large pre-B cells were C3bR+, 35 to 48% of small pre-B, 60 to 80% of immature B, and 99% of mature B cells. Mature plasma cells were rarely C3bR+. Myelomonocytic cells acquire C3bR relatively late during their development, with neutrophils beginning to express C3bR during the band stage of differentiation. All adult blood myelomonocytic lineage cells, identified by the monoclonal antibody MMA and by morphology, were C3bR+.
Animals↗
Human B cell differentiation. IV. Effect of monoclonal anti-immunoglobulin M and D antibodies on B cell proliferation and differentiation induced by T cell factors.
Monoclonal anti-mu and anti-delta antibodies and mixed lymphocyte reaction-derived T cell factors (MLR-TF) were examined alone and in combination for their effects on proliferation and differentiation of human B cells. MLR-TF induced proliferation and subsequent plasma cell differentiation of blood B cells without additional stimulation. The monoclonal anti-mu and anti-delta antibodies alone did not induce proliferation, but each was capable of augmenting B cell proliferation induced by MLR-TF. In contrast, the anti-mu antibody inhibited the MLR-TF induction of IgM plasma cell differentiation but did not affect the differentiation of IgG and IgA plasma cells. The anti-delta antibody had no effect on MLR-TF-induced plasma cell differentiation. Studies using density gradient separation of B cell subpopulations suggest that MLR-TF induce low-density B cells to proliferate and differentiate into plasma cells but that by themselves MLR-TF have little effect on B cells of relatively high density. The latter subpopulation of small resting B cells responded with proliferation to MLR-TF when combined with either the anti-mu or the anti-delta antibody, but these stimuli were insufficient for induction of terminal plasma cell differentiation.
Animals↗
Monoclonal antibody characterization of surface antigens in childhood T-cell lymphoid malignancies.
Although childhood T-cell acute lymphocytic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL) have certain clinical features in common, T-ALL carries a notably poorer prognosis than does T-NHL. To determine whether the malignant cells from patients with these disorders are distinguishable, we examined bone marrow and/or blood from 51 children with T-ALL and tumor biopsy specimens from 17 with T-NHL, using a panel of monoclonal antibodies directed against T-cell differentiation antigens. We found considerable phenotypic heterogeneity in both T-ALL and T-NHL. Of the T-ALL (defined by greater than 25% blasts in the bone marrow) patients, 33% demonstrated a surface antigen pattern consistent with the earliest thymocyte stage of T-cell development (T9+ and/or T10+, or T6-/T4-/T8-/T3-), 37% were of a midthymocyte stage (T6+, and/or simultaneous expression of T4-helper and T8-suppressor antigens), and 30% expressed surface antigen patterns found on mature thymocytes (T3+, variable expression of other antigens). In contrast, tumor cell phenotypes in the 17 T-NHL patients were approximately equally distributed between mid- and mature thymocyte phenotypes. No NHL samples were classified as the early thymocyte phenotype. Clinical features as related to specific T-ALL immunophenotypes are presented, and the implications of these findings in regard to the current understanding of the differences in tumor biology between T-ALL and T-NHL are discussed.
Antibodies, Monoclonal↗
B-cell differentiation.
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Antibodies, Monoclonal↗
Usefulness of monoclonal antibodies in the diagnosis and monitoring of patients with primary immunodeficiencies: combined experience in three clinical immunology centers.
Circulating levels of T-cell subsets and NK cells were determined in 78 patients with primary immunodeficiencies, 35 children with recurrent respiratory infections, and healthy age-matched controls. Normal T cell and natural killer (NK) cell values were observed in individuals with immunoglobulin A (IgA) deficiency and X-linked agammaglobulinemia, while reduced OKT4/OKT8 cell ratios and low levels of 5/9+ T helper cells were found in approximately 60% of patients with common variable immunodeficiency. Infants with severe combined immunodeficiency (SCID) and lymphopenia had virtually no cells expressing T-cell or NK-cell surface antigens, but had normal numbers of monocytes and other types of blood cells. Infants with DiGeorge syndrome, other primary T-cell defects, or SCID with B cells had few or no circulating cells of mature T helper-suppressor phenotypes, but had normal numbers of NK cells (HNK-1+) and NK function. These results support the idea of a common stem cell precursor for T, B, and NK cells, each of which follows a separate pathway of differentiation. Profound alterations were observed in the distribution and function of T-cell subsets in ataxia-telangiectasia patients who were previously shown to have thymic dysplasia. A significant reduction in the frequencies of OKT3+ and OKT4+ cells was observed in children with frequent respiratory infections during infancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Agammaglobulinemia↗
Interleukin 2 receptor expression by activated HNK-1+ granular lymphocytes: a requirement for their proliferation.
A subpopulation of HNK-1+ cells was found to express interleukin 2 receptor (IL 2R) as monitored by the anti-Tac monoclonal antibody after lectin or allogeneic cell stimulation. When blood mononuclear cells were stimulated with phytohemagglutinin (PHA) or concanavalin A for 3 days, or with pokeweed mitogen or allogeneic mononuclear cells for 6 days, virtually all of the HNK-1+ cells remained as small resting lymphocytes. One-fourth of these HNK-1+ cells expressed IL 2R, however, usually within 18 hr after stimulation. Neither circulating HNK-1+ cells nor unstimulated HNK-1+ cells in short-term culture expressed IL 2R. Only the subset of HNK-1+ cells that expressed T cell surface markers, such as the sheep erythrocyte receptor and Leu-4 antigen, could be induced to express IL 2R. When long-term cultures of HNK-1+ cells were established with initial PHA stimulation and the continued presence of IL 2, a majority of the cells was found to express the IL 2R. When anti-Tac antibody was added to the long-term cultures, proliferation of the HNK-1+ cells was completely inhibited. These results suggest that entry into growth cycle by this subpopulation of HNK-1+ granular lymphocytes may require two signals: a relatively nonspecific ligand interaction with cell surface glycoprotein(s) to induce expression of IL 2R, and subsequent IL 2 interaction with these specific cell surface receptors.
Adult↗
Cutaneous lymphoblastic lymphoma with pre-B markers.
Two children with cutaneous convoluted lymphoblastic lymphoma are reported. Malignant cells from both patients contained cytoplasmic Mu heavy chains characteristic of pre-B-cells and expressed CALLA and la antigens as well. Most cases of convoluted lymphoblastic lymphoma are T-cell-derived neoplasms. The non-T, non-B phenotype found in these two children demonstrates that histology does not necessarily predict immunophenotype. The association of the pre-B phenotype with cutaneous lymphoma has not been previously reported, but may represent a unique clinical-histopathologic-immunologic entity that occurs in young children.
Antibodies, Monoclonal↗
Differentiation of B lineage cells from liver of neonatal mice: generation of immunoglobulin isotype diversity in vitro.
The development and differentiation of B cells expressing different immunoglobulin (Ig) isotypes was studied in cultures of murine neonatal liver cells. Before culture, 5 to 15% of the liver cells were mu + pre-B cells; 1 to 3% had surface IgM and less than 0.1% had slgG. During 4 days in culture the number of pre-B cells declined, whereas the number of IgM B cells increased greater than 20-fold; IgG B cells also increased in number. Of the four subclasses, IgG3+ and IgG2b+ cells predominated, each representing 3 to 10% of the total B cells at day 4. IgG1+ and IgG2a+ cells were present in lower numbers, representing 1 to 5% and 0.3 to 2.5% of B cells, respectively. Most IgG+ cells also expressed sIgM. Only a minority (less than 10%) of the sIgM+ cells were sIgD+, and most sIgG+ cells were sIgD-. Few T cells were present in these cultures (less than 0.5% in newborn liver), and sIgG+ cells were generated in normal frequencies in cultures of cells from nude mice. The numbers of B cells expressing each IgG subclass were similar in cultures from athymic nu/nu mice, nu/+ heterozygous littermates, and normal BALB/c mice. Plasmablasts and plasma cells appeared over a 14-day culture interval, and these expressed cytoplasmic IgM, IgG3, IgG1, IgG2b, IgG2a, and IgA. Measurable amounts of the first four isotypes were detected in the culture supernatants by radioimmunoassay. These results indicate that neonatal B cells can undergo isotype switching in the absence of T cell help, and that the expression of sIgD may not be a prerequisite for cells to switch Ig isotypes.
Animals↗
Developmental immunology and the immunodeficiency diseases.
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Adolescent↗
Immunoglobulin VH determinants defined by monoclonal antibodies.
Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts.
Animals↗
New views of the immunoglobulin heavy-chain switch.
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Animals↗