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C Arpin

Publications and source records attributed to C Arpin.

At least 19 recordsLinked to original sources

Effects of T3R alpha 1 and T3R alpha 2 gene deletion on T and B lymphocyte development.

Thyroid hormones bind to several nuclear receptors encoded by T3R alpha and T3R beta genes. There is now accumulating evidence that thyroid hormones act on the immune system. Indeed, mice deficient for thyroid hormones show a reduction in lymphocyte production. However, the mechanisms involved and, in particular, the role of the different thyroid hormone receptors in lymphocyte development have not been investigated. To address that question, we have studied lymphocyte development in mice deficient for the T3R alpha 1 and T3R alpha 2 gene products. A strong decrease in spleen cell numbers was found compared with wild-type littermates, B lymphocytes being more severely affected than T lymphocytes. A significant decrease in splenic macrophage and granulocyte numbers was also found. In bone marrow, a reduction in CD45+/IgM- pro/pre-B cell numbers was found in these mice compared with wild-type littermates. This decrease seems to result from a proliferation defect, as CD45+/IgM- cells incorporate less 5-bromo-2'-deoxyuridine in vivo. To define the origin of the bone marrow development defect, chimeric animals between T3R alpha-/- and Rag1-/- mice were generated. Results indicate that for B cells the control of the population size by T3R alpha 1 and T3R alpha 2 is intrinsic. Altogether, these results show that T3R alpha 1 or T3R alpha 2 gene products are implicated in the control of the B cell pool size.

Animals↗

Impact of an urban effluent on antibiotic resistance of riverine Enterobacteriaceae and Aeromonas spp.

In order to evaluate the impact of an urban effluent on antibiotic resistance of freshwater bacterial populations, water samples were collected from the Arga river (Spain), upstream and downstream from the wastewater discharge of the city of Pamplona. Strains of Enterobacteriaceae (representative of the human and animal commensal flora) (110 isolates) and Aeromonas (typically waterborne bacteria) (118 isolates) were selected for antibiotic susceptibility testing. Most of the Aeromonas strains (72%) and many of the Enterobacteriaceae (20%) were resistant to nalidixic acid. Singly nalidixic acid-resistant strains were frequent regardless of the sampling site for Aeromonas, whereas they were more common upstream from the discharge for enterobacteria. The most common resistances to antibiotics other than quinolones were to tetracycline (24.3%) and beta-lactams (20.5%) for Enterobacteriaceae and to tetracycline (27.5%) and co-trimoxazole (26.6%) for Aeromonas. The rates of these antibiotic resistances increased downstream from the discharge at similar degrees for the two bacterial groups; it remained at high levels for enterobacteria but decreased along the 30-km study zone for Aeromonas. Genetic analysis of representative strains demonstrated that these resistances were mostly (enterobacteria) or exclusively (Aeromonas) chromosomally mediated. Moreover, a reference strain of Aeromonas caviae (CIP 7616) could not be transformed with conjugative R plasmids of enterobacteria. Thus, the urban effluent resulted in an increase of the rates of resistance to antibiotics other than quinolones in the riverine bacterial populations, despite limited genetic exchanges between enterobacteria and Aeromonas. Quinolone resistance probably was selected by heavy antibiotic discharges of unknown origin upstream from the urban effluent.

Aeromonas↗

Memory CD44(int) CD8 T cells show increased proliferative responses and IFN-gamma production following antigenic challenge in vitro.

F5 TCR transgenic mice challenged in vivo with peptide generate long-lived primed CD8 T cells that hyper-proliferate in response to peptide in vitro. These primed CD8 T cells can be subdivided into three distinct populations on the basis of CD44 cell surface expression. In this report, we show that among primed CD8 T cells, those expressing intermediate levels of CD44 appear to be true memory T cells by the measurement of a variety of characteristics. Indeed, these cells hyper-proliferate in response to peptide re-stimulation in vitro, and produce IFN-gamma with faster kinetics and at higher levels than naive populations in vitro. We also show that CD8 T cells expressing high levels of CD44 express several activation markers and cycle in vivo in the absence of antigen. However, this population is unable to respond to peptide stimulation in vitro as measured by both proliferation and IFN-gamma secretion. The origin and specificity of these cells is unknown. These results provide evidence that memory CD8 T cells are functionally different from naive CD8 T cells both in terms of proliferation and cytokine secretion. They identify the CD8/CD44(int) T cells as the population responsible for hyper-reactivity in vitro.

Animals↗

Presence of mefA and mefE genes in Streptococcus agalactiae.

Eighteen unrelated clinical isolates of Streptococcus agalactiae with the M phenotype harbored an mef gene. DNA sequencing showed that one of nine strains contained mefA (producing one amino acid substitution), whereas the remaining eight carried mefE (identity, 100%). Restriction analysis of PCR products indicated that the nine other strains also contained mefE.

Bacterial Proteins↗

Molecular characterization of TEM-59 (IRT-17), a novel inhibitor-resistant TEM-derived beta-lactamase in a clinical isolate of Klebsiella oxytoca.

A clinical isolate of Klebsiella oxytoca (Kox 443) was found to have a low-level resistance to broad-spectrum penicillins (MICs of amoxicillin and ticarcillin, 256 and 32 microg/ml, respectively), without substantial potentiation by 2 microg of clavulanic acid per ml (amoxicillin- and ticarcillin-clavulanate, 128 and 8 microg/ml, respectively), while being fully susceptible to cephalosporins and other beta-lactam antibiotics. These resistances were carried by a ca. 50-kb conjugative plasmid that encodes a single beta-lactamase with a pI of 5.6. Compared to TEM-2, this enzyme exhibited a 3- to 30-fold higher Km and a decreased maximal hydrolysis rate for beta-lactams; higher concentrations of suicide inactivators (5- to 500-fold higher concentrations giving a 50% reduction in hydrolysis) were required for inhibition. Nucleotide sequence analysis revealed identity between the blaTEM gene of Kox 443 and the blaTEM-2 gene, except for a single A-to-G change at position 590, leading to the amino acid change from Ser-130 Gly. This mutation has not been reported previously in the TEM type beta-lactamases produced by clinical strains, and the novel enzyme was called TEM-59 (alternative name IRT-17). This is the first description of an inhibitor-resistant TEM-derived enzyme in the species K. oxytoca.

Aged↗

The normal counterpart of IgD myeloma cells in germinal center displays extensively mutated IgVH gene, Cmu-Cdelta switch, and lambda light chain expression.

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre-B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased lambda light chain expression and a Cmu-Cdelta isotype switch. Using surface markers, we have previously isolated a population of surface IgM-IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased lambda light chain expression and a C&mu-Cdelta isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.

B-Lymphocytes↗

Dendritic cells enhance the differentiation of naïve B cells into plasma cells in vitro.

We have shown previously that in vitro-generated human dendritic cells have an effect on the response of B cells at various stages of their differentiation. In a culture system described for the in vitro induction of plasma-cell differentiation, it was reported that naïve B cells have a poor propensity to differentiate into plasma cells. In such a culture system, 12% of naïve B cells differentiated into plasma cells in the presence of IL-2 and IL-10, despite the interruption of CD40 signalling which is necessary for plasma-cell differentiation. However, as reported herein, naïve B cells differentiated fully into plasma cells in response to dendritic cells. Addition of dendritic cells enhanced this differentiation strikingly by recruiting 57% of B cells as plasma cells producing IgM, but also IgG and IgA. In this model, dendritic cells act in synergy with IL-2 at an early stage of CD40-dependent B-cell differentiation, while IL-2 and IL-10 act together, at a later stage, in the generation of plasma cells in a CD40-independent manner. Thus, in addition to the key role played by dendritic cells in the initiation of T-cell responses, our results suggest that dendritic cells regulate humoral responses.

B-Lymphocytes↗

Molecular characterization of a TEM-21 beta-lactamase in a clinical isolate of Morganella morganii.

A clinical isolate of Morganella morganii, with reduced susceptibility to expanded-spectrum cephalosporins and aztreonam, was found to produce an extended-spectrum beta-lactamase with a pI of 6.4. The nucleotide sequence of the encoding gene was that of the gene encoding TEM-21. This is the first molecular characterization of an extended-spectrum beta-lactamase in M. morganii.

Base Sequence↗

Memory B cells are biased towards terminal differentiation: a strategy that may prevent repertoire freezing.

Isolation of large numbers of surface IgD+CD38- naive and surface IgD-CD38- memory B cells allowed us to study the intrinsic differences between these two populations. Upon in vitro culture with IL-2 and IL-10, human CD40-activated memory B cells undergo terminal differentiation into plasma cells more readily than do naive B cells, as they give rise to five- to eightfold more plasma cells and three- to fourfold more secreted immunoglobulins. By contrast, naive B cells give rise to a larger number of nondifferentiated B blasts. Saturating concentrations of CD40 ligand, which fully inhibit naive B cell differentiation, only partially affect that of memory B cells. The propensity of memory B cells to undergo terminal plasma cell differentiation may explain the extensive extra follicular plasma cell reaction and the limited germinal center reaction observed in vivo after secondary immunizations, which contrast with primary responses in carrier-primed animals. This unique feature of memory B cells may confer two important capacities to the immune system: (a) the rapid generation of a large number of effector cells to efficiently eliminate the pathogens; and (b) the prevention of the overexpansion and chronic accumulation of one particular memory B cell clone that would freeze the available peripheral repertoire.

Animals↗

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↗

Molecular epidemiology of an outbreak due to extended-spectrum beta-lactamase-producing enterobacteria in a French hospital.

Between June 1992 and June 1993, 128 extended-spectrum beta-lactamase-producing enterobacteria (123 Klebsiella pneumoniae, 3 Escherichia coli, 1 Enterobacter aerogenes, and 1 Citrobacter diversus) were collected in a French university hospital. These isolates were recovered mainly from patients hospitalized in intensive care and neurosurgery units. The 128 strains were divided into 14 antibiotypes (ATBs; ATB1 to ATB14); 102 of 103 nonredundant isolates were shown to produce an SHV-4-related extended-spectrum beta-lactamase (pl 7.8, hybridization with a blaSHV probe); the remaining strain (Kp 2108) produced a TEM-3-related extended-spectrum beta-lactamase (pl 6.3, hybridization with a blaTEM probe). For representative isolates, five plasmid profiles (Pl to Pll-4), eight ribotypes (E1 to E8), and seven arbitrarily primed polymerase chain reaction profiles (A1 to A7) were obtained. The results suggest the spread of an epidemic strain of Klebsiella pneumoniae (E1, A1, Pl, various ATBs) from an intensive care unit throughout the hospital. Another epidemic strain (E2, A2, pl, ATB4) was confined to the neurosurgery unit. Other extended-spectrum beta-lactamase-producing Klebsiella pneumoniae of ribotypes distinct from E1 or E2 might result from the spread of an epidemic plasmid, such as reported for isolates of other enterobacterial species. Conversely, they might represent imported cases, such as the strain Kp 2108, which produced a TEM-3-related beta-lactamase.

Cross Infection↗

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↗