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Biomedical subjects

A Dziarski

Publications and source records attributed to A Dziarski.

10 recordsLinked to original sources
PubMed1985

B-cell activation in human plasma cell dyscrasias.

We studied the abnormal in vitro polyclonal B-cell activity observed in patients with multiple myeloma and Waldenström's macroglobulinaemia. Numbers of cells spontaneously secreting immunoglobulin (Ig) in freshly isolated suspensions of peripheral blood mononuclear cells and pokeweed mitogen (PWM) stimulated cultures of blood mononuclear cells were determined with a protein A reverse haemolytic plaque assay. These data were correlated with both the clinical and laboratory parameters of disease. Furthermore, Ig secreted into supernatants of PWM-stimulated cultures was examined by a light chain radioimmunoassay for evidence of in vitro activation of malignant B-cells. The mean level of circulating immunoglobulin secreting cells (IgSC) in patients was elevated when compared to that of normal subjects. The highest values were observed in those patients with the highest levels of serum paraprotein. However, experiments with cycloheximide suggested that such increased circulating IgSC values were often caused by the detection of Ig passively adsorbed to blood mononuclear cells. The studies with PWM stimulation of blood mononuclear cells were particularly revealing. Cultures of patient blood mononuclear cells with PWM showed depressed IgSC responses as a group compared to cultures of normal blood mononuclear cells; nevertheless, approximately half the patients demonstrated a sizeable response to PWM. No evidence for preferential activation of Ig secretion by the malignant B-cell clone was observed. Impaired PWM induced responses were associated with advanced or progressive clinical disease.

Adult↗
PubMed1984

Thymic B-cell activation in myasthenia gravis.

We studied secretion of immunoglobulin (Ig) by freshly isolated and pokeweed mitogen (PWM)-stimulated thymus cells and blood mononuclear cells in patients with myasthenia gravis (MG) and control subjects undergoing elective cardiac surgery. We used a protein A reverse hemolytic plaque assay to enumerate cells secreting IgG, IgM, and IgA (IgSC), and an ELISA assay for measuring IgG secreted into culture supernatants. We found that freshly isolated suspensions of MG thymus cells, compared with control thymus cells, contained increased numbers of cells that spontaneously secreted immunoglobulin. Thymus mononuclear cells from control as well as MG patients appeared capable of B-cell differentiation responses when stimulated by PWM. PWM-induced responses were greater in thymic than in autologous blood mononuclear cells in some MG patients and controls, although B cells were much less frequent in suspensions of thymic cells than blood cells. Thus, the thymus provides a favorable milieu for differentiation of its few B cells. In MG, the thymus may be a site of accentuated in vivo B-cell activation, as evidenced by increased numbers of resident IgSC.

Adolescent↗
PubMed1983

Staphylococcal peptidoglycan: T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes.

Staphylococcal cell wall products have been widely examined as probes for dissection of in vitro human immune responses. Mitogenic and polyclonal B-cell-activating properties have been attributed to intact cell walls or the protein A constituent thereof. We now report that staphylococcal peptidoglycan (PG), the major cell wall constituent, is not only a potent mitogen but also a polyclonal B-cell activator for human peripheral blood mononuclear cells (PBM). PG-induced proliferative responses of human PBM were comparable to that observed in pokeweed mitogen-stimulated cultures. As was true for pokeweed mitogen, PG-induced proliferation required the presence of T-cell help. Cultures of human PBM with PG also resulted in B-cell differentiation as reflected by an increase in numbers of immunoglobulin-secreting cells in stimulated cultures. In contrast to the proliferative response, PG-induced B-cell differentiation was relatively T-cell independent. This point became apparent when B-cell fractions were partially depleted of excessive numbers of monocytes before culture. Also, B-cell proliferation did not appear to be a major prerequisite for PG-induced B-cell differentiation responses. These data indicate that PG is a potent T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes.

B-Lymphocytes↗
PubMed1983

Human monocyte functional heterogeneity: monocyte fractionation by discontinuous albumin gradient centrifugation.

Human monocytes subserve many roles in the immune response. It is not clear, however, whether this functional heterogeneity reflects the action of different monocyte subpopulations. We separated human blood monocytes into distinct populations using a discontinuous (15-35%) serum albumin gradient technique. We examined if any of a number of monocyte functions were preferentially expressed by these five monocyte subsets. Monocytes in the 25% and 30% albumin fractions possessed more Fc (IgG) and C3 receptor activity than did monocytes in either of the 15, 20 or 35% fractions. In addition, monocytes isolated in the more dense albumin fractions were enriched for the capacity to support pokeweed mitogen-induced B-cell differentiation. All gradient fractions were equally capable of binding Raji cells and inhibiting Raji cell incorporation of [3H]thymidine. These data indicate that fractionation of monocytes by a discontinuous albumin gradient is an effective method to enrich for those monocytes with certain functional characteristics.

B-Lymphocytes↗
PubMed1982

Modulation of polyclonal B cell differentiation by human leucocyte alpha interferon.

Although interferon (IFN) profoundly affects immune responses in animals, less is known about its immunoregulatory activity in man. Therefore, peripheral blood mononuclear cells (PBM) from 20 healthy volunteers were incubated with pokeweed mitogen (PWM) in the presence and absence of human leucocyte alpha interferon (IFN alpha). In 18/20 experiments, IFN alpha added at initiation of culture markedly suppressed PWM-induced generation of immunoglobulin secreting cells (IgSC). IFN alpha suppressed proliferative responses in all experiments but the degree of suppression was not correlated with concomitant suppression of IgSC responses. Suppressive activity was resistant to pH 2 treatment but sensitive to treatment with trypsin. Delayed addition of IFN alpha was associated with decreased suppression. Suppression was not due to non-specific cytotoxicity since we observed (1) comparable viabilities in cultures with or without IFN alpha and (2) negligible effect when IFN alpha was added for the final 24 hr of culture. The data confirm previously described effects of IFN on mitogen stimulated PBM and, more importantly, provide convincing evidence that IFN alpha regulates human B cell functions.

B-Lymphocytes↗
PubMed1981

Polyclonal B-cell activity in myasthenia gravis.

Using a protein A-reverse hemolytic plaque assay, we found that some patients with myasthenia gravis have increased numbers of circulating immunoglobulin secreting cells (IgSC). This pattern was not related to drug therapy, age, sex, duration of symptoms, thymectomy, or serum levels of AChR antibody, although elevated IgSC values tended to occur in patients with active symptoms. The responses of peripheral blood mononuclear cells to pokeweed mitogen were normal. These data suggest increased in vivo polyclonal B-cell activation in some myasthenic patients, although in vitro polyclonal B-cell activation is normal.

Acetylcholine↗
PubMed1981

Heterogeneity of polyclonal B-cell activity in systemic lupus erythematosus.

We have examined the abnormal in vitro polyclonal B-cell activity observed in patients with systemic lupus erythematosus (SLE) using a staphylococcal protein A reverse hemolytic plaque assay. We have found the mean level of circulating immunoglobulin secreting cells (IgSC) in 30 SLE patients to be significantly elevated compared to that of normal subjects, although half of the SLE patients fell within the normal range. Cultures of SLE peripheral blood mononuclear cells (MC) stimulated with optimal or suboptimal doses of pokeweek mitogen (PWM) showed depressed IgSC responses as a group, compared to cultures of normal MC (p less than 0.005), although a fraction of patients had normal responses. In 11 of 30 SLE patients, IgSC were less numerous in stimulated than in unstimulated cultures, whereas all normal subjects showed augmented IgSC response in stimulated cultures (p less than 0.005). Impaired in vitro response was not due to (1) altered PWM induced activation, (2) aberrant kinetic response or (3) decreased survival in culture of SLE MC. Of note, altered IgSC responses did not appear to reflect antecedent in vivo B-cell activation. Numbers of circulating IgSC and PWM-induced IgSC were not correlated with clinical and serological indices of disease activity or status of corticosteroid therapy. These data indicate considerable heterogeneity with respect to polyclonal B-cell activity in SLE, and provide further insight into the relationships of in vivo and in vitro B-cell activation in patients with this disease.

Antibody-Producing Cells↗
PubMed1980

Mitogenic responsiveness of mouse, rat and human lymphocytes to Staphylococcus aureus cell wall, teichoic acid, and peptidoglycan.

The mitogenic activity of Staphylococcus aureus peptidoglycan (PG), teichoic acid (TA) and cell wall (CW, a PG-TA complex) for mouse, rat and human lymphocytes was determined by measuring DNA synthesis. At optimal concentrations PG was the most potent mitogen, inducing maximum stimulation of mouse spleen lymphocytes on day 2 of culture, rat spleen lymphocytes on day 3, rat lymph node cells on day 2, human peripheral blood lymphocytes on day 5, and human cord blood lymphocytes on day 4. CW was less mitogenic than PG for mouse splenocytes and human peripheral and cord blood lymphocytes, with maximum stimulation occurring on days 2, 6 and 5, respectively. CW was not mitogenic for rat lymphocytes, and TA was not mitogenic for mouse, rat and human lymphocytes. At high concentrations CW and TA were cytotoxic, as indicated by markedly reduced thymidine uptake and low viability. PG was not toxic to lymphocytes. Our results suggest that TA when bound to PG can at high concentrations mask the mitogenic activity of PG and render CW cytotoxic.

Animals↗
PubMed1979

Mitogenic activity of staphylococcal peptidoglycan.

Staphylococcus aureus peptidoglycan displayed a marked dose-dependent mitogenic activity for mouse splenocytes and human peripheral blood lymphocytes in vitro, as measured by increased [3H]thymidine incorporation. Similarly it was mitogenic for athymic nude mouse spleen cells, whereas no blastogenic effect was observed in T cell-enriched and B cell-depleted mouse lymphocyte cultures. These data demonstrate that peptidoglycan-responding cells in mouse spleen cell cultures are B lymphocytes.

Animals↗