PubMed Health⌕ Search

PubMed · 1902854

Complement subcomponent C1q stimulates Ig production by human B lymphocytes.

Abstract

The regulation of Ig production by human B lymphocytes is a complex process involving interactions among B cells, APC, T lymphocytes and soluble factors including activation, growth, and differentiation factors. Components of the complement system, including C3a, C3b, C3d, and C5a, have been shown to influence various stages in this process. In this study, we demonstrate that the C1q subcomponent of complement binds to both small resting and large activated B cells and stimulates immunoglobulin production by Staphylococcus aureus Cowan-activated tonsillar B lymphocytes. This effect is present whether C1q is added to the B cells either at the beginning or near the end of a 7-day culture period and is not associated with enhancement of proliferation. The C1q stimulation of Ig production is, however, associated with increased steady state levels of mRNA for the mu Ig H chain. Furthermore, C1q stimulated IgM production by the human B cell line SKW 6.4, which is capable of secreting IgM in response to B cell differentiation factors (BCDF). SLE is a disorder frequently associated with polyclonal activation of B lymphocytes. We studied the effect of C1q on B cells from two patients with this disorder and one with an SLE-like illness, all selected for the predominance of either IgM or IgG in serum. Spontaneous or BCDF-stimulated Ig secretion was of the isotype predominant in vivo, whereas C1q selectively stimulated B cells to produce the other isotype (IgG vs IgM). Thus, C1q interacts with B lymphocytes in a manner distinct from that of BCDF found in mixed lymphocyte supernatants. C1q may be an important factor influencing the production of Ig by B lymphocytes in normal individuals and in patients with abnormalities of B cell activity.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

K R Young, J L Ambrus, A Malbran, A S Fauci, A J Tenner. 1991-05-15. Complement subcomponent C1q stimulates Ig production by human B lymphocytes.. https://pubmed.ncbi.nlm.nih.gov/1902854/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA.

B-cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells that are resistant to apoptosis as a result of bcl2 oncogene overexpression. Studies were done to determine the mechanism for the up-regulation of bcl-2 protein observed in CD19+ CLL cells compared with CD19+ B cells from healthy volunteers. The 11-fold higher level of bcl-2 protein in CLL cells was positively correlated with a 26-fold elevation in the cytosolic level of nucleolin, a bcl2 mRNA-stabilizing protein. Measurements of the bcl2 heterogeneous nuclear/bcl2 mRNA (hnRNA)/mRNA ratios and the rates of bcl2 mRNA decay in cell extracts indicated that the 3-fold higher steady-state level of bcl2 mRNA in CLL cells was the result of increased bcl2 mRNA stability. Nucleolin was present throughout the nucleus and cytoplasm of CLL cells, whereas in normal B cells nucleolin was only detected in the nucleus. The addition of recombinant human nucleolin to extracts of normal B cells markedly slowed the rate of bcl2 mRNA decay. SiRNA knockdown of nucleolin in MCF-7 cells resulted in decreased levels of bcl2mRNA and protein but no change in beta-actin. These results indicate that bcl-2 overexpression in CLL cells is related to stabilization of bcl2 mRNA by nucleolin.

B-Lymphocytes↗

Interleukin-16 inhibits immunoglobulin e production by B lymphocytes.

BACKGROUND: The increased production of IgE is a hallmark of atopic disorders. CD4+ T cells regulate the production of Immunoglobulin (Ig) E by B cells. Interleukin (IL) 16, a CD4+ specific cytokine, is highly expressed at sites of allergic inflammation. Our aim was to determine the effect of IL-16 on IgE production in atopic subjects. METHODS: Freshly isolated peripheral blood mononuclear cells (PBMC) from atopic subjects were stimulated with recombinant IL (rIL) 4 and anti-CD40 antibody to promote IgE production in the presence or absence of rIL-16 added at different time intervals prior to stimulation. The levels of IgE in cell culture supernatants collected at day 14 were measured by ELISA. The effect of IL-16 on the expression of the Cepsilon transcript was evaluated by reverse-transcription polymerase chain reaction. To evaluate whether the modulatory effect of IL-16 on IgE production was mediated by interferon-gamma (IFN-gamma), anti-CD40/IL-4-stimulated PBMC were cultured in the presence of rIL-16 and neutralizing concentrations of anti-IFN-gamma antibody. RESULTS: PBMC stimulated with rIL-4 (400 U/ml) and anti-CD40 monoclonal antibody (0.5 microg/ml) produced significant amounts of IgE (range: 1.3-46.0 ng/ml). The addition of rIL-16 twenty-four hours before stimulation significantly reduced the levels of IgE released by anti-CD40/IL-4-stimulated PBMC (0.5-29.6 ng/ml, p < 0.05). IL-16 reduced the expression of the Cepsilon transcript in stimulated PBMC. IL-16 induced the expression of IFN-gamma mRNA. However, the use of anti-IFN-gamma antibody did not alter the effect of IL-16 on IgE production. Rescue doses of IL-13 did not restore the production of IgE by PBMC treated with IL-16. IL-16 did not alter IgE production in CD14-depleted cell preparations suggesting that the IL-16-mediated effects on IgE production may be related to CD14+ cells. CONCLUSION: These data show that IL-16 inhibits IgE production and therefore may play an important regulatory role in atopic disorders.

B-Lymphocytes↗

"Virtual flow cytometry" of immunostained lymphocytes on microscopic tissue slides: iHCFlow tissue cytometry.

BACKGROUND: A method and approach is developed for fully automated measurements of immunostained lymphocytes in tissue sections by means of digital color microscopy and patent pending advanced cell analysis. The validation data for population statistic measurements of immunostained lymphocytes in tissue sections using tissue cytometry (TC) is presented. The report is the first to describe the conversion of immunohistochemistry (IHC) data to a flow cytometry-like two parameter dot-plot display, hence the technique is also a virtual flow cytometry. We believe this approach is a paradigm shift, as well as novel, and called the system iHCFlow TC. Seven issues related to technical obstacles to virtual flow cytometry (FC) are identified. DESIGN: Segmentation of a 512 x 474 RGB image and tabular display of statistical results table took 12-15 s using proprietary developed algorithms. We used a panel of seven antibodies for validation on 14 cases of mantle cell lymphoma giving percentage positive, total lymphocytes, and staining density. A total of 2,027 image frames with 810,800 cell objects (COBs) were evaluated. Antibodies to CD3, CD4, CD8, Bcl-1, Ki-67, CD20, CD5 were subjected to virtual FC on tissue. The results of TC were compared with manual counts of expert observers and with the results of flow cytometric immunophenotyping of the same specimen. RESULTS: The correlation coefficient and 95% confidence interval by linear regression analysis yielded a high concordance between manual human results (M), FC results, and TC results per antibody, (r = 0.9365 M vs. TC, r= 0.9537 FC vs. TC). The technical issues were resolved and the solutions and results were evaluated and presented. CONCLUSION: These results suggest the new technology of TC by iHCFlow could be a clinically valid surrogate for both M and FC analysis when only tissue IHC is available for diagnosis and prognosis. The application for cancer diagnosis, monitoring, and prognosis is for objective, rapid, automated counting of immunostained cells in tissues with percentage results. We report a new paradigm in TC that converts IHC staining of lymphocytes to automated results and a flow cytometry-like report. The dot plot histogram display is familiar, intuitive, informative, and provides the pathologists with an automated tool to rapidly characterize the staining and size distribution of the immunoreactive as well as the negative cell population in the tissue. This systems tool is a major improvement over existing ones and satisfies fully the criteria to perform Cytomics (Ecker and Tarnok, Cytometry A 2005;65:1; Ecker and Steiner, Cytometry A 2004;59:182-190; Ecker et al., Cytometry A 2004;59:172-181).

B-Lymphocytes↗