The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
Animals ; B-Lymphocytes ; immunology ; pathology ; Humans ; Inflammation ; immunology ; pathology ; Receptors, Notch ; immunology ; Signal Transduction ; immunology ; T-Lymphocytes ; immunology ; pathology

T cell immunity and phagocytic activity were studied in the blood of patients with IgA nephropathy in order to clarify their roles in the pathogenesis of IgA nephropathy. The percentages of total T lymphocytes, helper T cell and suppressor T cells were significantly reduced in patients. A significantly elevated helper T cell/suppressor T cell ratio in patients showed a predominant reduction in suppressor T cells. There was a significant relationship between histologic findings and helper T cell/suppressor T cell ratio in patients. Natural Killer (NK) cell activity was significantly reduced but the lymphocyte response after phytohemagglutinin (PHA) stimulation was not in patients. ConA-induced suppressor cell activity was not depressed despite of a decrease in suppressor T cells in patients. Phagocytic activity of polymorphonuclear leucocytes (PMNs) ingesting yeasts was significantly reduced in patients. Also an inverse correlation was found between serum IgA levels and phagocytic activity of PMN. It is concluded that suppressor T cell defects, depressed phagocytic activity and impaired NK cell activity may play a role in the pathogenesis of IgA nephropathy.
B-Lymphocytes/immunology ; Glomerulonephritis, IGA/*immunology/pathology ; Humans ; Killer Cells, Natural/immunology ; Neutrophils/immunology ; *Phagocytosis ; T-Lymphocytes/*immunology ; T-Lymphocytes, Regulatory/immunology

Adult ; Biopsy ; Fatty Liver ; complications ; immunology ; pathology ; Female ; Hepatitis B, Chronic ; complications ; immunology ; pathology ; Humans ; Male ; T-Lymphocytes, Regulatory ; immunology

Progressive multifocal leukoencephalopathy (PML) is a rare and lethal central nervous demyelinating disease caused by JC polyomavirus (JCV), particularly in patients with impaired immune system. The variation of JCV plays an important role in the pathogenesis of PML, including the recombination of non-coding regulatory region (NCCR), which is closely related to binding sites of transcription factors and affect the level of gene transcription. Nucleotide mutations in VP1 region determine the antigenicity and receptor specificity of JCV, play an important role in cell adsorption, immune-mediation and pathogenicity. In addition, immune cells are also involved in the pathogenesis of PML. T lymphocytes can recognize virus antigens, clear JCV, which are directly related to the prognosis of PML. B lymphocytes can serve as latent sites of JCV, and participate in viral transmission, replication, and coordination of the expression of transcription factors. This paper summarizes the roles of JCV variation and immune cells in pathogenesis of PML.
B-Lymphocytes ; immunology ; virology ; Capsid Proteins ; genetics ; immunology ; Humans ; JC Virus ; immunology ; Leukoencephalopathy, Progressive Multifocal ; pathology ; virology ; Mutation ; T-Lymphocytes ; immunology ; virology

<b>OBJECTIVEb>To induce anti-B-cell acute lymphoblastic leukemia (B-ALL) cytotoxic T lymphocyte response against immunoglobulin heavy chain frame-derived nonapeptide.

<b>METHODSb>The peptide, QLVQSGAEV, containing IgHV1 frame region 3rd-11th amino acids (IgHV1(3-11)), was synthesized. IgHV1(3-11)-T2 binding tests were performed. HLA-A * 0201-positive normal peripheral blood mononuclear cells (PBMNC) were stimulated by IgHV1(3-11)-loaded antigen presenting cells three times at weekly intervals. HLA-A * 0201/IgHV1(3-11) tetramers were used to detect the proliferation of IgHV1(3-11)-specific CD8(+) T cells in the culture. Seven IgHV gene families of B-ALL patients were respectively amplified by PCR and the PCR products were sequenced to select IgHV1 and IgHV3 family monoallelic functional rearrangements. Among them, HLA-A * 0201 positive individuals were subsequently identified. Cytotoxicity of IgHV1(3-11)-specific CD8(+) T cells against HLA-A * 0201-positive IgHV1/IgHV3 family B-ALL cells was measured by MTT assay.

<b>RESULTSb>The synthesized IgHV1(3-11) up-regulated HLA-A * 0201 expression on T2 cell surface by 1.63-folds. The percentage of IgHV1(3-11)-specific CD8(+) T cells in HLA-A * 0201-positive normal PBMNC was increased from 1.64% after second stimulation to 82.57% after third stimulation. At effector: target ratio of 20:1, the killing rate of IgHV1(3-11)-specific CD8(+) T cells against IgHV1 family B-ALL cells was 18.24%, being 1.8-folds as that against IgHV3 family B-ALL cells (P = 0.01).

<b>CONCLUSIONb>Cytolytic T lymphocytes generated in vitro against immunoglobulin heavy chain frame-derived nonapeptides can kill B-ALL cells expressing these peptides.

Cells, Cultured ; Humans ; Immunoglobulin Heavy Chains ; immunology ; pharmacology ; Leukemia, B-Cell ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology

After having successfully constructed and expressed the gene of the anti-CD3/anti-CD20 bispecific single-chain antibody (bscCD3 x CD20), here we analyzed its in vitro bioactivity of mediating the lysis of Ramous human B-lymphoma cells in the presence of T-enriched human peripheral blood lymphocytes (PBL). Obvious opoptosis characters were observed by Annexin V/PI(AV/PI) stained and scanning electron microscope. As evaluated by non-radioactive cytotoxity assay, the bscCD3 x CD20 showed potent bioactivity of mediating human B-lymphoma cells lysis in the presence of T-enriched human PBL. The potency of cytotoxicity depended on the ratios of effect cells to target cells (E:T) used. Further, the antibody showed a dose and time-dependent effect on mediating Ramous cells lysis. The specific lysis reached about 87.3% at an antibody concentration of 5microg/mL and E:T used at 10:1. Clear changes in apoptogenes expression profiles were detected by apoptosis gene array after Ramous cells were treated with the antibody and PBL. Among the upregulated apoptogenes, ATM and P53 showed an increase of 187 times and 15 times respectively, which suggested that ATM-p53 pathway may be the main apoptosis way of Ramous cells induced by T cells in the presence of the bscCD3 x CD20.
Antibodies, Bispecific ; immunology ; Antigens, CD20 ; immunology ; Apoptosis ; immunology ; CD3 Complex ; immunology ; Humans ; Lymphoma, B-Cell ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Cells, Cultured

To evaluate the expression of cytoplasmic CD79a (CyCD79a) and other commonly used B-lymphoid immunomarkers including cytoplasmic CD22 (CyCD22), CD19, CD20 and CD10 in various acute leukemia cells and to define the most sensitive and specific markers in the diagnosis of precursor B-cell acute lymphoblastic leukemia (pB-ALL), the immunophenotypic data from 221 de novo adult and pediatric acute leukemia patients as studied using multi-parameter flow cytometry in addition to routine morphologic and enzyme cytochemical assay, were retrospectively analyzed. Cytogenetic and/or molecular biological data in all 45 cases of acute promyelocytic leukemia (APL) and 13 cases of acute leukemia suspected as AML with the fusion genes such as AML1/ETO and CBFbeta/MYH11 were investigated. The results showed that CyCD79a and CyCD22 were the most sensitive and specific markers respectively for pB-ALL. Expression of CyCD79a was seen in 100% of 58 cases of pB-ALL. At the same time, none (0%) of all 147 cases of acute myeloid leukemia (AML) and 15 cases of precursor T-cell acute leukemia (pT-ALL) was positive for CyCD22. The conclusion is made that united detection of CyCD79a and CyCD22 is the optimal immune combination for the diagnosis pB-ALL and the distinguishing pB-ALL with AML and pT-ALL.
Acute Disease ; B-Lymphocytes ; immunology ; Biomarkers, Tumor ; immunology ; CD79 Antigens ; immunology ; Cytoplasm ; immunology ; Flow Cytometry ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Myeloid ; genetics ; immunology ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; pathology ; Sialic Acid Binding Ig-like Lectin 2 ; immunology

<b>OBJECTIVEb>To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia (IRP) and explore the action of B lymphocyte in the pathogenic mechanism of IRP.

<b>METHODSb>Quantities of whole B lymphocytes and CD5+ B lymphocytes as well as the expressions of Fas and Bcl-2 in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission (CR), and 10 normal controls were assayed by flow cytometry.

<b>RESULTSb>The percentages of B lymphocyte and CD5+ B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls (P < 0.05), and there was no significant difference between the latter two groups (P > 0.05). There was no significant difference of Fas expression in B lymphocyte among three groups (P > 0.05). The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls (P < 0.01), and significantly higher in CR patients than in normal controls (P < 0.01). The apoptosis-related index was significantly lower in untreated patients than in CR patients or normal controls (P < 0.05), and significantly lower in CR patients than in normal controls (P < 0.05). The percentage of B lymphocyte was positively correlated with post-treated response time (r = 0.53, P < 0.01).

<b>CONCLUSIONb>The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantities of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.

Adolescent ; Adult ; B-Lymphocytes ; cytology ; immunology ; Case-Control Studies ; Child ; Female ; Humans ; Lymphocyte Subsets ; Male ; Middle Aged ; Pancytopenia ; immunology ; pathology

B-Lymphocytes ; Child ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Precursor Cells, B-Lymphoid ; pathology

To test the European BIOMED-1 Concerted Action proposed technique to detect minimal residual disease (MRD) in the chinese patients with precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) by triple-staining flow cytometry and to define both normal and aberrant phenotypic profiles of precursor B cells, a series of bone marrow samples, 35 from precursor-B-ALL (13 in newly diagnosed cases, 15 at the end of remission induction therapy and 7 at end of the consolidations), and 19 from normal controls, were immunophenotyped with the five triple-staining antibodies (TdT/CD10/CD19, CD10/CD20/CD19, CD34/CD38/CD19, CD34/CD22/CD19 and CD19/CD34/CD45) recom-mended by the BIOMED-1 using common flow cytometric protocols. Further, with different ratios of the leukemic cells with CD34/CD38/CD19 phenotype and normal mononuclear cells, a serial dilution test was analyzed. The results showed that three major CD19(+) cell subpopulations were identified in the normal controls, representing three consecutive maturation stages. The subpopulations in the precursor-B-ALL cases disappeared and were replaced with a great number of luekemic cells which had different characteristics of phenotypes, and then they reappeared with almost same characteristics as the normal CD19(+) cells after the patients achieved complete remission. When the five triple-staining antibody combinations were used, the phenotypic aberrancies could be identified in 12/13 (92.3%) cases with newly diagnosed precursor-B-ALL, at least one triple-labeling per case at the level of 0.01% or more. The frequencies of phenotypic aberrations detected with the triple-staining were 8/13 (61.5%) for CD10/CD20/CD19, 5/13 (38.5%) for CD34/CD38/CD19, 4/13 (30.8%) for CD10/TdT/CD19, 3/13 (23.1%) for CD34/CD22/CD19, and 2/13 (15.4%) for CD34/CD45/CD19. At the end of remission induction, the phenotypic aberrancies could be detected in 5/15 (33.3%), of which, 3/8 (37.5%) cases with the leukemic phenotypes detected both at the newly diagnosis and at the end of induction. The dilution test indicated that the cells with CD34/CD38/CD19 detected by flow cytometry correlated well with the leukemic cells added (r = 0.85, P < 0.05) over 1:1 to 1:400,000. It is concluded that the flow cytometric detection of precursor-B-ALL-MRD proposed by BIOMED-1 Concerted Action were well realized in this study. The one precursor-B-ALL cell can be effectively detected out of 10(4) normal bone marrow cells.
Adolescent ; Adult ; Aged ; Antigens, CD ; analysis ; B-Lymphocytes ; immunology ; pathology ; Bone Marrow Cells ; immunology ; pathology ; Child ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Neoplasm, Residual ; blood ; immunology ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; blood ; immunology ; pathology