Dissection of the role of PfEMP1 and ICAM-1 in the sensing of Plasmodium-falciparum-infected erythrocytes by natural killer cells.

Background: Host innate immunity contributes to malaria clinical outcome by providing protective inflammatory cytokines such as interferon-gamma, and by shaping the adaptive immune response. Plasmodium falciparum (Pf) is the etiologic agent of the most severe forms of human malaria. Natural Killer (NK) cells are lymphocytes of the innate immune system that are the first effectors to produce interferon-gamma in response to Pf.

Clustering of pre-B cell integrins induces galectin-1-dependent pre-B cell receptor relocalization and activation.

Interactions between B cell progenitors and bone marrow stromal cells are essential for normal B cell differentiation. We have previously shown that an immune developmental synapse is formed between human pre-B and stromal cells in vitro, leading to the initiation of signal transduction from the pre-BCR. This process relies on the direct interaction between the pre-BCR and the stromal cell-derived galectin-1 (GAL1) and is dependent on GAL1 anchoring to cell surface glycosylated counterreceptors, present on stromal and pre-B cells.

Regulation of V(D)J recombination.

Adaptive immunity is intimately linked to the expression of antigen-specific immunoglobulin and T cell receptor genes and their recombination assembly from germline V, D and J gene segments. This developmentally regulated process relies on the activity of the Rag1-Rag2 recombinase, on accessibility of target gene segments and on monoallelic gene activation. Recent studies have revealed new mechanisms that, along with recombinase activity and locus accessibility, are likely to contribute to the control of V(D)J recombination, including target-site bias by the recombinase, RNA processing and chromosome positioning.

Initiation of pre-B cell receptor signaling: common and distinctive features in human and mouse.

B cell development in the bone marrow is a highly regulated process and expression of a functional pre-BCR represents a crucial checkpoint, common to human and mouse. In this review, we discuss pre-BCR analogies and differences between the two species leading to pre-B cell differentiation and proliferation. In addition, the mechanisms triggering pre-BCR activation are reviewed, taking into account the recent report of heparan sulfates and galectin 1 as stromal cell-derived pre-BCR ligands.

The chemosensitivity to therapy of childhood early B acute lymphoblastic leukemia could be determined by the combined expression of CD34, SPI-B and BCR genes.

We have identified genes differentially expressed in childhood early B acute lymphoblastic leukemia at diagnosis, according to chemosensitivity. Chemosensitive (M1) and chemoresistant (M3) patients present <5% and >25% of residual leukemic blasts at 21 days of treatment, respectively. The expression profiles of 4205 genes for 32 patients included in the FRALLE93 protocol have been determined using microarray.

Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate.

Macrophages and myeloid dendritic cells (DCs) represent alternative differentiation options of bone marrow progenitors and blood monocytes. This choice profoundly influences the immune response under normal and pathological conditions, but the underlying transcriptional events remain unresolved. Here, we show that experimental activation of the transcription factors PU.

Potassium permanganate as a probe to map DNA-protein interactions in vivo.

Potassium permanganate (KMnO4) has widely been used in genomic footprinting assays to map unusual gene structures, including the melting DNA block in transcriptional elongation that results from promoter-proximal pausing of RNA polymerase (Pol) II complexes. Although it has been assumed that DNA-bound proteins do not protect underlying nucleic acids from KMnO4 modifications, we provide evidence herein that this chemical can readily be used to detect nuclear factor loading at a promoter when using optimized conditions. Moreover, by comparing parallel KMnO4 and dimethylsulfate (DMS) in vivo footprintings, we show that the utilization of KMnO4 in combination with another chemical probe maximizes the detection of factor occupancy at a DNA regulatory region, thus providing a better opportunity to define the actual profiles of DNA-protein contacts at given genomic sites in living cells.

Alpha beta T-cell development is not affected by inversion of TCR beta gene enhancer sequences: polar enhancement of gene expression regardless of enhancer orientation.

V(D)J recombination and expression of the T-cell receptor beta (TCRbeta) gene are required for the development of the alphabeta T lymphocyte lineage. These processes depend on a transcriptional enhancer (Ebeta) which acts preferentially on adjacent upstream sequences, and has little impact on the 5' distal and 3' proximal regions of the TCRbeta locus. Using knock-in mice, we show that alphabeta T-cell differentiation and TCRbeta gene recombination and expression are not sensitive to the orientation of Ebeta sequences.

Expression profiling in mouse fetal thymus reveals clusters of coordinately expressed genes that mark individual stages of T-cell ontogeny.

To search for genes that participate in regulatory networks sustaining mouse embryonic T-cell development, we have performed expression profiling using nylon macroarrays. Labeled samples representative of individual developmental stages were utilized, taking advantage of cell homogeneity during early thymus ontogeny. cDNAs revealing differential expression were further selected using labeled samples derived from lymphoid versus non-lymphoid tissues, and from mutant thymi exhibiting T-cell developmental defects.

Wdr12, a mouse gene encoding a novel WD-Repeat Protein with a notchless-like amino-terminal domain.

The WD-repeat protein family consists of a large group of structurally related yet functionally diverse proteins found predominantly in eukaryotic cells. These factors contain several (4-16) copies of a recognizable amino-acid sequence motif (the WD unit) thought to be organized into a "propeller-like" structure involved in protein-protein regulatory interactions. Here, we report the cloning of a mouse cDNA, referred to as Wdr12, which encodes a novel WD-repeat protein of 423 amino acids.

Regulation of T cell function by NK cell receptors for classical MHC class I molecules.

Inhibitory receptors for MHC class I molecules were initially characterised on NK cells. Human and mouse NK cell receptors (NKRs) are also expressed on T cells, predominantly on a subset of memory-phenotype CD8(+) T cells. This review focuses on the precise determination of interactions between NKRs and MHC class I, as well as on the unexpected in vivo function of NKRs on T cells.

Cell surface expression of surrogate light chain (psi L) in the absence of mu on human pro-B cell lines and normal pro-B cells.

Surrogate light chains (psi L) encoded by lambda-like (lambda 5) and VpreB genes play a critical role in controlling the early steps of B cell differentiation. We prepared new anti-VpreB monoclonal antibodies (mAb) (3C7/6F6) which preferentially recognize the VpreB epitope at the cell surface of human cell lines that do not express the mu chain. These mAb provide the first characterization of human pro-B cell lines expressing surface psi L.

Composite exon structure of an unusual Ig lambda-like gene located at human 22q11 position.

The surrogate light chain, composed of the VpreB and the lambda-like proteins, plays a critical role in controlling the early stages of B lymphocyte development. The lambda-like locus, located on the q11. 2-q11.