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Y J Liu

Publications and source records attributed to Y J Liu.

At least 91 records · Page 5Linked to original sources
PubMed1997

Germinal center founder cells display propensity for apoptosis before onset of somatic mutation.

B lymphocytes undergo affinity maturation of their antigen receptors within germinal centers. These anatomical structures develop in secondary lymphoid organs from the clonal expansion of a few antigen-specific founder B cells, whose isolation and characterization are reported here. Human germinal center founder cells express the naive B cell markers surface IgM and IgD as well as the germinal center B cell markers CD10 and CD38. They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture. The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones. Unmutated sIgM+IgD-CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.

ADP-ribosyl Cyclase↗
PubMed1997

Follicular dendritic cells specifically express the long CR2/CD21 isoform.

This paper describes an antibody (mAb 7D6) that specifically recognizes human follicular dendritic cells (FDCs). By expression cloning, a cDNA clone encoding for the long human CR2/ CD21 isoform (CD21L) that contains an additional exon (10a) was isolated. We demonstrated that FDCs selectively express CD21L, while B cells selectively express the short CR2/CD21 lacking exon 10a (CD21S). By screening mouse Ltk- cells transfected with the CD21L cDNA, we further showed that the other two anti-human FDC mAbs DRC-1 and KiM4 also recognize CD21L. Thus, CD21L represents the first characterized human FDC-specific molecule, which may confer unique functions of FDCs in germinal center development.

Animals↗
PubMed1997

Human interdigitating dendritic cells directly stimulate CD40-activated naive B cells.

Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40+ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC also showed weak nonspecific esterase staining and had the ability to induce an allogeneic mixed lymphocyte reaction. In this study, we further show that in the presence of surrogate activated T cells in the form of CD40 ligation and IL-2, IDC enhance the proliferation of naive B cells and induce their differentiation into plasma cells producing IgM. Evidence for the anatomical co-localization of naive B cells and IDC in the T cell area together with the data obtained in vitro implies a role for IDC in the initiation of the extrafollicular reaction.

B-Lymphocytes↗
PubMed1997

Molecular cloning of human RP105.

RP105 is a 105-kDa type I membrane protein of the leucine-rich repeat (LRR) family. Anti-RP105 sensitizes B cells to antigen-receptor-mediated apoptosis, but protects B cells from radiation-induced apoptosis and stimulates B cell proliferation. The sequence of the mouse RP105 has been reported. Here, we report the characterization of the human RP105. The 2.6-kb cDNA encodes a protein of 661 amino acids which displays 78% homology with mouse RP105. The 22 LRR and the 9 potential N-linked glycosylation sites within the extracellular region are conserved. While previous studies have shown that RP105 is expressed on surface IgM+IgD+2 B cells in mice, human RP105 was shown to be expressed on all subsets of mature B cells and dendritic cells. Human RP105 gene was mapped to the long arm of chromosome 5, where numerous cytokines and receptors have been localized.

Animals↗
PubMed1997

Polymerase chain reaction-based identification of a novel serpin from human dendritic cells.

A subtraction library of CD40-stimulated human tonsil dendritic cells has been constructed using a polymerase chain reaction approach adapted for low numbers of cells. From this library we identified a cDNA for a serine protease inhibitor, a serpin, which is absent from monocytes, B cells and T cells but expressed in CD40-activated monocyte- and progenitor cell-generated dendritic cells. In addition, the serpin is expressed in a lung fibroblast cell line and keratinocytes. Its mRNA is detected only in tonsil and thymus. The serpin described here reportedly functions as a megakaryocyte maturation factor in the presence of interleukin (IL)-3 and IL-11. This suggests that dendritic cells may promote the immune response by protecting IL-3 and IL-11 or other essential proteins from degradation.

Amino Acid Sequence↗
PubMed1997

Regulation of B-cell commitment to plasma cells or to memory B cells.

During humoral immune responses, B-lymphocyte activation is followed by differentiation along either the plasma cell pathway or the memory B-cell pathway. Recent studies suggest that CD40-CD40 ligand, OX-OX40 ligand, a group of cytokines and intracellular transcriptional factors may all contribute to B-lymphocyte differentiation control.

Animals↗
PubMed1997

Computerised prostate boundary estimation of ultrasound images using radial bas-relief method.

A new method is presented for automatic prostate boundary detection in ultrasound images taken transurethrally or transrectally. This is one of the stages in the implementation of a robotic procedure for prostate surgery performed by a robot known as the robot for urology (UROBOT). Unlike most edge detection methods, which detect object edges by means of either a spatial filter (such as Sobel, Laplacian or something of that nature) or a texture descriptor (local signal-to-noise ratio, joint probability density function etc.), this new approach employs a technique called radial bas-relief (RBR) to outline the prostate boundary area automatically. The results show that the RBR method works well in the detection of the prostate boundary in ultrasound images. It can also be useful for boundary detection problems in medical images where the object boundary is hard to detect using traditional edge detection algorithms, such as ultrasound of the uterus and kidney.

Humans↗
PubMed1997

Sex-specific effects of growth hormone on hepatic 11beta-hydroxysteroid dehydrogenase activity and gene expression in hypothyroid rats.

To investigate the effects of growth hormone (GH) on 11beta-HSD1, we determined changes in hepatic 11beta-HSD1 activity in hypothyroid rats following treatment with subcutaneous (s.c) injection of GH for periods ranging from 24 h to 7 days. In male rats, hypothyroidism markedly reduced the hepatic 11beta-HSD1 activity and serum testosterone levels (p < 0.01). Subcutaneous injection of GH once daily to male hypothyroid rats for 48 h inhibited hepatic 11beta-HSD1 activity. However, the same daily dose of GH administered to male hypothyroid rats for 7 days, resulted in a marked increase in hepatic 11beta-HSD1 activity and gene expression (p < 0.01). Furthermore, daily s.c injections of GH to castrated male hypothyroid rats for 7 days reduced hepatic 11beta-HSD1 activity rather than inducing it, the same response seen in hypothyroid female rats. In addition, the treatment of castrated male hypothyroid rats with testosterone for 7 days significantly increased this enzyme activity (p < 0.01). The changes in hepatic 11beta-HSD1 were demonstrated to be associated with the testes in hypothyroid male rats following treatment with GH for 7 days. Moreover, the prolonged exposure to GH required to induce hepatic 11beta-HSD1 in intact hypothyroid male rats and the lack of a similar effect in castrated male hypothyroid rats suggests that this action is indirect and that it may be mediated by androgen production from Leydig cells of the testes and induced by the daily injections of GH. Treatment of hypothyroid male rats with GH at 6-h intervals, however, feminized the hepatic 11beta-HSD1 gene expression.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Oscillatory Ca2+ signaling in somatostatin-producing cells from the human pancreas.

Oscillatory Ca2+ signaling was studied in human somatostatin-releasing pancreatic delta cells identified by immunostaining. A ratiometric fura-2 technique was used for measuring cytoplasmic concentrations of Ca2+ and Sr2+ in delta cells exposed to the respective cation. Rhythmic activity in terms of slow (frequency, 0.1 to 0.4 per minute) oscillations from close to the basal level was seen in the presence of 3 to 20 mmol/L glucose during superfusion with medium containing 2.6 to 5 mmol/L Ca2+ or 5 mmol/L Sr2. These oscillations could be transformed into a sustained increase by decreasing extracellular Ca2+ or adding 1 mmol/L tolbutamide or 20 nmol/L glucagon. Addition of glucagon to a medium containing 20 mmol/L glucose resulted in the generation of short (< 30 seconds) transients, which disappeared upon exposure to 100 nmol/L of the intracellular Ca(2+)-adenosine triphosphatase (ATPase) inhibitor thapsigargin. When analyzing small aggregates of islet cells, it became evident that oscillatory activity in delta cells can be synchronous with that in adjacent non-delta cells. It is concluded that secretion of pancreatic somatostatin in man involves Ca2+ signaling similar to that regulating the pulsatile release of insulin.

Adult↗
PubMed1997

Store-operated Ca2+ entry in insulin-releasing pancreatic beta-cells.

The fluorescent indicator Fura-2 was used to characterize the store-operated Ca2+ entry in insulin-releasing pancreatic beta-cells. To avoid interference with voltage-dependent Ca2+ entry, the cells were hyperpolarized with 400 microM diazoxide and the channel blocker methoxyverapamil was also present in some experiments. The cytoplasmic Ca2+ concentration ([Ca2+]j) of hyperpolarized mouse beta-cells was strikingly resistant to changes in external Ca2+. In cells exposed to 20 mM glucose, stimulation with 100 microM carbachol induced an initial [Ca2+]j peak followed by a sustained increase due to store-operated influx of the cation. Store-operated influx was also induced by the intracellular Ca(2+)-ATPase inhibitor thapsigargin. In the presence of store-operated influx, [Ca2+]j became markedly sensitive to variations in external Ca2+, but this sensitivity was blocked by La3+. In beta-cells exposed to both Ca2+ and Mn2+ there was slow Mn2+ quenching of the Fura-2 fluorescence, which was accelerated upon stimulation of store-operated influx. This acceleration was reversed by glucose-stimulated filling of the internal Ca2+ stores. The store-operated Ca2+ entry increased markedly during culture of the beta-cells. Activation of protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol-13 acetate, inhibition of serine/threonine phosphatase by okadaic acid and inhibition of tyrosine kinase by genistein had little effect on the store-operated influx of Ca2+. In beta-cells equilibrated in 5 mM Sr2+, carbachol exposure resulted in a pronounced cytoplasmic Sr2+ ([Sr2+]j) peak due to intracellular mobilization, but little or no sustained elevation. Moreover, after activating the store-operated pathway by exposure to thapsigargin, variations in extracellular Sr2+ between 0-2 mM had only marginal effects on [Sr2+]j. Although the store-operated influx apparently accounts for a minor fraction of the Ca2+ entry, its depolarizing influence may under certain conditions be up-regulated with resulting distortion of the beta-cell function.

Animals↗
PubMed1997

Normal human B cell sub-populations and their malignant counterparts.

Seven tonsillar B cell sub-sets have been isolated according to cell surface molecular markers. The molecular characteristics of their phenotype, cell cycle, survival, somatic mutations and isotype switch status permit their inter-relationships to be followed up until the plasma cell stage. Different lymphoma types correlate with all except one of the stages and only two out of nine non-Hodgkin's B cell lymphomas cannot be presently associated to a normal peripheral B cell sub-set. The assignment of lymphomas to their normal human B cell counterparts will facilitate the identification of the causative event(s) responsible for the malignant transformation.

B-Lymphocyte Subsets↗
PubMed1997

Mechanisms of selection and differentiation in germinal centers.

The choice between death and survival, a feature of early B cell development, is a choice also faced by mature B cells. If they survive this early developmental decision, mature B cells then face a second choice: either to undergo either terminal differentiation into plasma cells or to differentiate into memory B cells. Antigens, T cell signals (cytokines, CD40 ligand and Fas ligand) as well as the activation state of B cells determine their ultimate fate.

B-Lymphocytes↗
PubMed1997

Cross-linking of antigen receptor via Ig-beta (B29, CD79b) can induce both positive and negative signals in CD40-activated human B cells.

Antigen-dependent activation of B lymphocytes is mediated through surface immunoglobulins and their associated molecules Ig-alpha (CD79a, Mb1) and Ig-beta (CD79b, B29). Here we show that an antibody directed against the extracellular part of human Ig-beta can, when cross-linked by CD32-transfected L cells, induce an IL-2-dependent proliferation of tonsil B cells. With the use of L cells stably transfected with both CD32 and CD40L, anti-Ig-beta activation of B cells was combined with CD40 triggering, an important component of the T cell-dependent B cell activation. This dual cellular activation resulted in two different phases, with initially synergistic proliferative effects, both without and with IL-2 or IL-10. Then, after 5-6 days of culture, cells stimulated with both anti-Ig-beta and CD40L underwent massive cell death, in contrast to B cells activated with CD40L alone. Cell death was not prevented by the addition of IL-2 or IL-10, but was prevented by the addition of IL-4. These results are discussed in the context of positive and negative selection of mature B cells.

Animals↗
PubMed1997

Germinal center development.

Using a set of surface markers including IgD and CD38, human tonsillar B cells were classified into discrete subpopulations. Molecular and functional analysis allowed us to identify: i) two sets of naive B cells (Bm1 and Bm2); ii) germinal center founder cells (Bm2'); iii) an obscure population of germinal center B cells, displaying a high load of somatic mutations in IgV genes, C mu to C delta switch and preferential Ig lambda light chain usage: these cells may represent the precursors of normal and malignant IgD-secreting plasma cells; iv) the centroblasts (Bm3) in which somatic mutation machinery is activated; v) the centrocytes (Bm4) in which isotype switch occurs; vi) the memory B cells. The characterization of these subpopulations showed that: i) programmed cell death is set before somatic mutations, possibly providing an efficient way for affinity maturation; ii) only high affinity centrocytes are allowed to switch isotype; iii) CD40-ligation inhibits plasmacytic differentiation of mature B lymphocytes; iv) memory B cells preferentially differentiate into plasma cells; v) IgD isotype switch occurs in normal B cells; vi) receptor editing may be induced by somatic mutations in germinal centers. We also characterized two types of antigen-presenting cells in germinal centers: follicular dendritic cells that select high affinity B cells, and a new subset of germinal center dendritic cells that activate germinal center T cells.

Animals↗
PubMed1997

Oscillatory signaling and insulin release in human pancreatic beta-cells exposed to strontium.

Oscillatory signaling and insulin release were studied in isolated pancreatic islets and beta-cells obtained from human cadaveric organ donors. Taking advantage of Sr2+ as an analog for Ca2+, it was possible to demonstrate glucose-induced rhythmic activity in individual beta-cells identified by immunostaining. Glucose-induced slow oscillations of Sr2+ (frequency, 0.1-1.0/min) were sometimes seen at a sugar concentration as low as 3 mM. Addition of 20 nM glucagon resulted in a broadening of the oscillations or in their transformation into sustained elevation. Moreover, the presence of glucagon resulted in the appearance of short transients of Sr2+, which disappeared after exposure to the intracellular Ca2+-adenosine triphosphatase inhibitor thapsigargin. Digital image analyses indicated that slow oscillations can be synchronized among cells in small aggregates and intact islets. The rhythmic activity in the glucose-stimulated beta-cell had its counterpart in pulsatile insulin release when single islets were perifused with a Sr2+-containing medium. It is concluded that the human beta-cell has oscillatory signaling for insulin release similar to that observed in experimental animals.

Adult↗
PubMed1997

[A study on expression of the heat shock suppressed gene in distal organs of rats after scalding].

In order to address the question whether stress in intact higher animals may induce cellular heat shock response in distal organs, the inhibition of normal gene expression was studied on the basis of our previous findings about the induction of heat shock proteins in liver and brain of rats after scalding. Male SD rats were scalded on the back, 10-240 min thereafter decapitated, and the heat shock suppressed gene-1 was quantitated by dot blotting. The results showed that gene-1 decreased rapidly after scalding in both the organs, and did not recover to control levels even 240 min after scalding. The decrease of gene-1 went parallell with the severity of scalding. Thus it may be concluded that stress may induce heat shock response of distant organs in intact animals. Possible pathological significance of these findings was discussed.

Animals↗