Increase In IgG Synthesis Research Articles

Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors.

Generalized DNA hypomethylation contributes to altered T cell function and gene expression in systemic lupus erythematosus (SLE). Some of the overexpressed genes participate in the disease process, but the full repertoire of genes affected is unknown. Methylation-sensitive T cell genes were identified by treating T cells with the DNA methyltransferase inhibitor 5-azacytidine and comparing gene expression with oligonucleotide arrays. CD70, a costimulatory ligand for B cell CD27, was one gene that reproducibly increased. We then determined whether CD70 is overexpressed on T cells treated with other DNA methylation inhibitors and on SLE T cells, and determined its functional significance. Oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction, and flow cytometry were used to compare CD70 expression in T cells treated with 2 DNA methyltransferase inhibitors (5-azacytidine and procainamide) and 3 ERK pathway inhibitors known to decrease DNA methyltransferase expression (U0126, PD98059, and hydralazine). The consequences of CD70 overexpression were tested by coculture of autologous T and B cells with and without anti-CD70 and measuring IgG production by enzyme-linked immunosorbent assay. The results were compared with those of T cells from lupus patients. SLE T cells and T cells treated with DNA methylation inhibitors overexpressed CD70 and overstimulated B cell IgG production. The increase in IgG synthesis was abrogated by anti-CD70. SLE T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. This increased B cell costimulation and subsequent immunoglobulin overproduction may contribute to drug-induced and idiopathic lupus.

Vestibular Neuronitis —Serum and CSF Virus Antibody Titer—

The cerebrospinal fluid (CSF) findings of patients with vestibular neuronitis were virologically evaluated and discussed in contrast to those of herpes zoster. CSF samples obtained from seven patients with vestibular neuronitis, aged 28 to 55 years, were examined. The results were as follows: The CSF protein level in the vestibular neuronitis showed the peculiar change; i.e. its level was normal at the onset period of vertigo, but it rose to abnormal levels mostly in the period of two weeks, while the cell count remained normal throughout all phases of our study. Herpes simplex virus (HSV) type 1 IgG antibody titers measured by indirect immunofluorescent antibody technique (IF) in paired sera rose in one of the seven cases of vestibular neuronitis, but the antibody titers of the same virus in the CSF were not detected. HSV type 1 IgG antibody titers measured by IF in the CSF were detected in two of seven cases of vestibular neuronitis, but not significant. The ratio of EB virus (EBV) capsid antigen IgG antibody titers in CSF to that in serum ranged from 1:160 to 1:80 in vestibular neuronitis. There was no direct available evidence that vestibular neuronitis caused a break in blood-CSF barrier, an increase in IgG synthesis in the central nervous system or active infection with HSV, varicella zoster virus (VZV), or EBV. In this paper, we summarized the recent information on studies of the CSF and a latent herpes virus infection in order to give perspective to the pathogenesis of vestibular neuronitis.

Lymphocyte phenotype and function in chronically transfused children with sickle cell disease.

Immunologic studies were performed on mononuclear cells from ten chronically transfused children with sickle cell disease, and the results were compared with those from five other groups: 21 sickle cell patients who were not receiving regular transfusions, 6 chronically transfused children with other forms of refractory anemia, 10 previously splenectomized children, 5 boys with hemophilia A, and 27 normal adult controls. The helper:suppressor T cell ratios (T4:T8) in all groups except hemophiliacs were normal, were unrelated to the number of units transfused, and were not suggestive of findings reported for patients with the acquired immune deficiency syndrome (AIDS) or groups at risk for the syndrome. Percentages of T3, T4, and T8 cells were low in sickle cell and splenectomized patients, but not in chronically transfused patients with other anemias. Serum IgG was frequently elevated, and IgG synthesis in vitro was increased relative to IgM synthesis in sickle cell patients. Coculture experiments indicated that such findings may stem from a selective increase in IgG synthesis by B cells. Thus, transfused sickle cell patients have a particular pattern of immunologic abnormalities that is distinct from that seen in AIDS.

The role of cobalamin in synthesis of protein and immunoglobulins by human peripheral lymphocytes

The effects of vitamin B 12 (cobalamin, Cb1) on IgG synthesis were measured in human peripheral blood lymphocytes (PBL) cultured for 6 days in the presence of pokeweed mitogen. The synthesis and release of total protein and IgG were measured by precipitation of the proteins in the media that had incorporated 3H leucine. Cells from 5 Cbl deficient donors synthesized and released less protein and IgG than cells from healthy donors. Large amounts of free Cbl added in vitro enhanced the synthetic capacities of the Cbl deficient cells but not the normal cells. Cells from 6 healthy donors were somewhat depleted of Cbl in vitro by culture in the absence of any source of Cbl. When Cbl was added there was a significant enhancement of protein synthesis, but the increase in IgG synthesis, while considerable, did not reach significance. No effect of deficiency of Cbl or the addition of Cbl was observed on cell replication or blastogenesis. Apparently Cbl has an effect on protein and IgG synthesis and release by human PBL in addition to any potential effect on DNA synthesis and cell division.

Age-Related Changes in the Subsets and Functions of Human T Lymphocytes

Abstract The purpose of this study was to investigate changes in immunocompetence associated with aging in humans by the use of various immunologic parameters. Volunteers examined in this study were healthy or apparently healthy without diseases affecting the immune system and ranged from 14 to 89 years of age. The results of this study are summarized in Table I. The absolute number of peripheral blood lymphocytes (PBL) decreased with aging. The mean count was 2043 in the adult group (less than 60 years of age) and 1659 in the aged group (over 60 years of age). When T lymphocytes were assayed by rosette formation with neuraminidase-treated sheep erythrocytes in the presence of fetal calf serum after 1 hr incubation at 4°C, there was no difference in the proportions of T lymphocytes between the groups, whereas the proportions of T cells as assayed by rosette formation with sheep erythrocytes in the absence of fetal calf serum were significantly depressed in the aged group (p < 0.01). On the other hand, the proportion of T lymphocytes assayed by rosette formation with sheep erythrocytes after centrifugation at 1500 RPM for 5 min at room temperature was higher in the aged group than in the adult group (p < 0.02). The proportion of IgG-Fc receptor-bearing T lymphocytes detected by double rosette formation with sheep erythrocytes and chicken erythrocytes sensitized with rabbit IgG antibody was also higher in the aged than in the adult group (p < 0.05). The proportion of complement receptor-bearing lymphocytes did not change with aging. In addition, the proportion of surface Ig-bearing lymphocytes examined after being treated in pH 4.0 acetate buffer for 1 min to remove nonspecifically bound Ig from the cell surface showed no differences between the two groups. Response to PHA and concanavalin A was impaired in the aged (aged 70 to 83 years) compared to the young adult group (aged 20 to 40 years) (p < 0.01), whereas the response to pokeweed mitogen was of the same magnitude. PHA response was negatively correlated with the proportion of IgG-Fc receptor-bearing T cells. The mixed lymphocyte culture reaction with mitomycin-treated AL1 cells derived from Burkitt's lymphoma was also impaired in the aged group (p < 0.01) as was cell-mediated cytotoxicity to AL1 cells as target cells (p < 0.05). Levels of IgG and IgA in plasma were significantly higher in the aged than in the adult group (p < 0.001), whereas those of IgM and IgE were not different. Radioimmunoassay determination of Ig classes revealed that the geometric means of IgG, but not IgM or IgA, synthesized in vitro was significantly increased in the aged compared to the young adult group (p < 0.05) when PBL were cultured in the presence of PWM for 7 days. This increase in IgG synthesis in the aged group was attributed to enhanced T helper activity.