<b>OBJECTIVEb>To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.

<b>METHODSb>The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.

<b>RESULTSb>The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).

<b>CONCLUSIONSb>Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.

Humans ; Immunohistochemistry ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; Macrophages ; physiology ; Prognosis ; T-Lymphocytes, Regulatory ; physiology

<b>OBJECTIVEb>To develop chromosome abnormal karyotype quality control cell and to explore the external quality assessment (EQA) method for chromosome karyotype analysis.

<b>METHODSb>The chromosome abnormal karyotype quality control cells were prepared by EB virus (EBV) transfection of human B lymphocyte strain establishment and were distributed to participating labs for EQA test of chromosome karyotype analysis project at appointed time. The evaluation results were obtained through 4 grades scoring.

<b>RESULTSb>Six kinds of chromosome abnormal karyotype quality control cells were initially developed, the karyotypes of which were 46,X, t(Y;5)(q12;q21), 46, XY, 15p +, 46, XX, t(13;18)(q12;q21), 46, X, r(Xp), 46,X,t(Y;Y), 46,XX,t(9;20)(p13;p13) respectively. In the external quality assessment, feedbacks from the participating labs on the sequencing results of the six kinds of quality control cells showed that the wholly overlapping rate were 82.1%, 92.0%, 84.6%, 80.8%, 86.2%, 74.1% and the wholly deviation rate were 10.7%, 8.0%, 11.5%, 19.2%, 13.8%, 18.5%. The overall wholly overlapping rate, partial overlapping rate, partial deviation rate and wholly deviation rate turned out to be 83.2%, 0.6%, 2.5% and 13.7% respectively.

<b>CONCLUSIONb>The misdiagnose rate of chromosome karyotype analysis is rather high and regular external quality assessment is necessary to achieve dynamic information and improve diagnosis quality.

B-Lymphocytes ; virology ; Cell Line ; Chromosome Aberrations ; Chromosome Painting ; Herpesvirus 4, Human ; physiology ; Humans ; Karyotyping ; methods ; Lymphocytes ; virology

Childhood minimal change nephrotic syndrome (MCNS) has often been associated with allergic symptoms such as urticaria, bronchial asthma, atopic dermatitis, allergic rhinitis and elevated IgE levels and referred to involve immune dysfunction. Fc epsilon RII is known to be involved in IgE production and response. Interleukin-4 is being recognized as a major cytokine up-regulating IgE production. Hence the present study is aimed at investigating the role of interleukin-4 and Fc epsilon RII in the pathogenesis of MCNS. IgE was measured by ELISA. Fc epsilon RII was analyzed by fluorescence activated cell scanner (FAC-scan) by double antibody staining with anti Leu16-FITC and anti Leu20-PE. Soluble IgE receptor was measured by ELISA using anti CD23 antibody (3-5-14). Interleukin-4 activities were measured by CD23 expression on purified human tonsillar B cells. Serum IgE levels were significantly higher in MCNS (1,507 +/- 680 IU/dl) than in normal controls (123 +/- 99.2 IU/dl). A significantly higher expression of membrane Fc epsilon RII was noted for MCNS (41 +/- 12%) than that in normal controls (18 +/- 6.2%) (p < 0.001). Soluble CD23 levels were also significantly higher in MCNS (198 +/- 39.3%) than in normal controls (153 +/- 13.4) (p < 0.01). Interleukin-4 activity in sera of MCNS (12U/ml) was also significantly higher than normal controls (4.5U/ml). These results indicate that increased production of Fc epsilon RII and interleukin-4 may play an important role in the pathogenesis of MCNS.
B-Lymphocytes/immunology ; Child ; Humans ; Immunoglobulin E/blood ; Interleukin-4/*physiology ; Nephrosis, Lipoid/*etiology/physiopathology ; Receptors, IgE/biosynthesis/*physiology ; Solubility

Current therapies for autoimmune diseases are not cures but merely palliatives, aimed at reducing symptoms. For the most part, these treatments provide nonspecific suppression of the immune system and thus do not distinguish between a pathogenic autoimmune response and a protective immune response. Recently emerging evidence not only has indicated the involvement of members of the TNF receptor/ligand superfamilies but also has revealed exciting innovative strategies for the treatment of autoimmune diseases and other chronic inflammatory diseases without depressing the immune response in general. In this review, we will discuss the regulatory mechanisms of TNF receptor/ligand family members, such as HVEM/ LIGHT, 4-1BB/4-1BBL, and GITR/GITRL that regulate T and B cell functions and participate in the process of inflammatory diseases. We will also discuss how intervening in the costimulatory pathways mediated by these molecules might have some potential as a therapeutic approach to immune disorders.
Animals ; Apoptosis ; Autoimmune Diseases/immunology/metabolism/pathology ; B-Lymphocytes/immunology/physiology ; Dendritic Cells/physiology ; Human ; Inflammation/*immunology ; Lymphocyte Activation/immunology ; Models, Biological ; Receptors, Tumor Necrosis Factor/*physiology ; T-Lymphocytes/immunology/physiology ; Tumor Necrosis Factor/immunology/*physiology

The oncogenic Epstein-Barr virus (EBV) -encoded latent membrane protein 1 (LMP1) enables this virus's long-term survival within the cells of immune system. Mean while, LMP1 also plays a critical role for the transformation of resting B cells by EBV. It initiates the activation of signalling pathways, such as NF-kappaB, mitogen-activated protein kinase (MAPK), and JAK/STAT cascade by adaptor proteins including the tumor necrosis factor (TNF) receptor associated factors (TRAFs) and the TNF receptor associated death domain protein (TRADD). It increases the expression of adhesion molecules LFA-1, ICAM-1, and costimulatory molecule B7-1 of B cells, and regulates the antibody and cytokine secreted by B cells. LMP1 and CD40 have many common properties in signal transduction. Both of them co-localize in lipid rafts for signal transduction. Considering its close relationship with CD40, the research on LMP1 has become a hot spot in the immunology field.
Animals ; B-Lymphocytes ; immunology ; CD40 Antigens ; genetics ; physiology ; Gene Expression Regulation, Viral ; Herpesvirus 4, Human ; genetics ; metabolism ; physiology ; Humans ; Signal Transduction ; Viral Matrix Proteins ; genetics ; physiology

<b>BACKGROUNDb>Several kinds of intercellular adhesion molecules closely relate to hepatitis B. The complex of CD(2) and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, hyperplasia and activation of T lymphocytes. In this study, we explored the relationship between the expression of CD58 in liver tissue and chronic hepatitis B infection.

<b>METHODSb>We determined the expression of the CD58 molecule on the surface of hepatocytes by using immunohistochemistry and the levels of serum HBV DNA from patients with HBV infection and from normal controls. The biochemical parameters of hepatic function were analyzed as well.

<b>RESULTSb>CD58 expression in hepatocytes significantly increased with the severity progression of chronic HBV infection. The IOD levels (log10) of CD58 in the control, mild, moderate, and severe chronic HBV infection groups were 0, (7.20+/-4.64) x 10(3), (25.63+/-7.41) x 10(3) and (37.47+/-11.17) x 10(3) respectively (P<0.05 compared with the control group, respectively).

<b>CONCLUSIONb>CD58 probably increases cell mediated immunity to eliminate hepatitis B virus and leads to damage of hepatocytes.

CD58 Antigens ; analysis ; DNA, Viral ; blood ; Hepatitis B, Chronic ; immunology ; Humans ; Immunohistochemistry ; Liver ; immunology ; physiopathology ; T-Lymphocytes ; physiology

B cell linker (BLNK) is a key linker protein of B cell receptor (BCR) signaling pathway. BLNK participates in the regulation of PLC-γactivity and the activation of Ras pathway through its typical structure and interaction network with other proteins, and is thus widely involved in the regulation of B cell proliferation, differentiation, apoptosis and signal transduction. Furthermore, it is closely related to anaphylactic diseases, multiple sclerosis, chromosomal aneuploidy, aneuglobulinemia, B lymphocytic leukemia and lymphoma. Herein we review the structure and biological function of BLNK and its role in B cell-related diseases. BLNK can cooperate with a series of effective proteins to activate BCR signaling pathway, thereby regulating the development, maturation and function of B cells. The functional mutation of BLNK can destroy the homeostasis of B cells and affect the development and maturation of B cells, which leads to the occurrence of B cell related diseases. A comprehensive understanding of the biological functions of BLNK not only provides insights into the pathogenesis of B cell-related diseases, but also inspires new ideas and helps to find breakthroughs for the treatment of these diseases with BLNK as the therapeutic target.
Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; physiology ; Apoptosis ; B-Lymphocytes ; cytology ; physiology ; Cell Differentiation ; Cell Proliferation ; Humans ; Mutation ; Receptors, Antigen, B-Cell ; chemistry ; physiology ; Signal Transduction ; Structure-Activity Relationship

<b>BACKGROUNDb>Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line.

<b>METHODSb>By using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometric analyses were performed to investigate the Sam68 functions.

<b>RESULTSb>A slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells.

<b>CONCLUSIONSb>The proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; physiology ; Animals ; B-Lymphocytes ; cytology ; immunology ; physiology ; Binding Sites ; genetics ; Blotting, Western ; Cell Cycle ; physiology ; Cell Death ; physiology ; Cell Growth Processes ; drug effects ; physiology ; Cell Line, Tumor ; Culture Media, Serum-Free ; pharmacology ; Mutation ; genetics ; Phosphorylation ; Proline ; genetics ; RNA-Binding Proteins ; genetics ; metabolism ; physiology ; Receptors, Antigen, B-Cell ; immunology ; physiology ; Signal Transduction ; drug effects ; physiology ; Tyrosine ; metabolism

The OPG/RANKL/RANK system plays an important role in osteoclastogenesis and represents a great progress in bone biology. RANKL, which expresses on the surface of osteoblast/stromal cells and activated T cells, binds to RANK on the osteoclastic precursors or mature osteoclasts, and promotes osteoclastogenesis and bone resorption. While osteoprotegerin (OPG), which is expressed by osteoblasts/stromal cells, strongly inhibits bone resorption by binding to its ligand RANKL and thereby blocks the interaction between BANKL and RANK. A number of cytokines and hormones exert their effects on bone metabolism by regulating the OPG/RANKL ratio in the bone marrow microenvironment. RANK is also expressed on mammary epithelial cells and RANKL expression in these cells is induced by pregnancy hormones, RANKL and RANK are essential for the formation of the lactating mammary gland and the transmission of maternal calcium to neonates in mammalian species. Modulation of these systems provides a unique opportunity to develop novel therapeutics to inhibit bone loss in osteoporosis, rheumatoid arthritis, and bone metastasis of cancer. Further research should be focused on the cooperation of OPG/RANKL/RANK system with other signal pathways and the interactions among bone remodeling, immune system and endocrinology system. Currently, the development of OPG analogues or compounds which may stimulate OPG expression is becoming an attractive industry which may be profitable to both patients and manufacturers.
Animals ; Bone Resorption ; immunology ; metabolism ; Humans ; Osteoclasts ; cytology ; metabolism ; pathology ; Osteogenesis ; drug effects ; genetics ; immunology ; Osteoprotegerin ; metabolism ; physiology ; RANK Ligand ; metabolism ; physiology ; Receptor Activator of Nuclear Factor-kappa B ; metabolism ; pharmacology ; physiology ; T-Lymphocytes ; drug effects ; immunology

Mouse spleen cells activated in a mixed lymphocyte reaction release a soluble factor, which induces a significant proliferative response in fresh mouse spleen cells. This proliferation inducing factor (PIF) was found to be heat stable (90 degrees C for 45 min) and also resistant to trypsin or chymotrypsin treatment. By using a sizing HPLC column, the molecular weight of PIF appears to be 25 kDa. Mouse spleen cells treated with anti-thy-1 + complement lost Con-A induced proliferative responses but responded well to PIF. B cell depleted spleen cells obtained by negative selection panning, did not respond to PIF. These results indicate that B cells proliferated in response to PIF. Polymixin-B, which blocks the B cell proliferative response to LPS, did not inhibit PIF induced proliferation.
Animal ; B-Lymphocytes/physiology* ; B-Lymphocytes/drug effects ; Bone Marrow/metabolism ; Cell Division/physiology ; Chromatography, High Pressure Liquid ; Chymotrypsin/pharmacology ; Dose-Response Relationship, Drug ; Growth Substances/pharmacology* ; Growth Substances/chemistry ; Heat ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Molecular Weight ; Polymyxin B/pharmacology ; Protein Denaturation ; Spleen/metabolism* ; Thymus Gland/metabolism ; Trypsin/pharmacology