Structure and selected properties of Al-Cr-Fe alloys with the presence of structurally complex alloy phases.

The aim of the study was to supplement the data on the AlCrFe alloy with binary phase structure and the AlCrFe alloy with multiphase structure prepared with two different cooling rates from the liquid state. The presence of the structurally complex AlCrFe phase was confirmed by neutron diffraction, scanning electron microscopy with the analysis of chemical composition and transmission electron microscopy. Additionally, the AlCr phase with γ-brass structure was identified for AlCrFe alloy in both cooling rates from the liquid state.

Using All-Atom Potentials to Refine RNA Structure Predictions of SARS-CoV-2 Stem Loops.

A considerable amount of rapid-paced research is underway to combat the SARS-CoV-2 pandemic. In this work, we assess the 3D structure of the 5' untranslated region of its RNA, in the hopes that stable secondary structures can be targeted, interrupted, or otherwise measured. To this end, we have combined molecular dynamics simulations with previous Nuclear Magnetic Resonance measurements for stem loop 2 of SARS-CoV-1 to refine 3D structure predictions of that stem loop.

Multi-therapeutic potential of autoantibodies induced by immune complexes trapped on follicular dendritic cells.

Induction of autoantibodies (autoAbs) targeting disease drivers / mediators is emerging as a potential immunotherapeutic strategy. Auto-immune complex (IC)-retaining follicular dendritic cells (FDCs) critically regulate pathogenic autoAb production in autoreactive germinal centers (GCs); however, their ability to induce potentially therapeutic autoAbs has not been explored. We hypothesized that deliberate display of clinically targeted antigens (Ags) in the form of ICs on FDC membranes induces target-specific autoreactive GCs and autoAbs that may be exploited therapeutically.

Structural characterization of the viral and cRNA panhandle motifs from the infectious salmon anemia virus.

Infectious salmon anemia virus (ISAV) has emerged as a virus of great concern to the aquaculture industry since it can lead to highly contagious and lethal infections in farm-raised salmon populations. While little is known about the transcription/replication cycle of ISAV, initial evidence suggests that it follows molecular mechanisms similar to those found in other orthomyxoviruses, which include the highly pathogenic influenza A (inf A) virus. During the life cycle of orthomyxoviruses, a panhandle structure is formed by the pairing of the conserved 5' and 3' ends of each genomic RNA.

Construction and testing of the instrument for neutron holographic study at the Budapest Research Reactor.

Neutron scattering device dedicated to neutron holography experiments is described. The device is operating at a constant wavelength prepared by a double focusing monochromator. It is equipped by highly efficient shielding, proper collimator, Eulerian cradle, monitor detector, gamma-ray, and neutron detectors as well.

Activation of B cells by antigens on follicular dendritic cells.

A need for antigen-processing and presentation to B cells is not widely appreciated. However, cross-linking of multiple B cell receptors (BCRs) by T-independent antigens delivers a potent signal that induces antibody responses. Such BCR cross-linking also occurs in germinal centers where follicular dendritic cells (FDCs) present multimerized antigens as periodically arranged antigen-antibody complexes (ICs).

IL-6 produced by immune complex-activated follicular dendritic cells promotes germinal center reactions, IgG responses and somatic hypermutation.

Reports that follicular dendritic cells (FDCs) produce IL-6 prompted the hypotheses that immune complexes (ICs) induce FDCs to produce IL-6 and that FDC-IL-6 promotes germinal center (GC) reactions, somatic hypermutation (SHM) and IgG production. FDCs were activated in vitro by addition of ICs and FDC-IL-6 production was determined. Wild-type (WT) and IL-6 knockout (KO) mice, as well as chimeras with WT and IL-6 KO cells, were immunized with (4-hydroxy-3-nitrophenyl)-acetyl (NP)-chicken gamma globulin (CGG) and used to study anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) responses, GC formation and SHM in the VH186.

T-independent antibody responses to T-dependent antigens: a novel follicular dendritic cell-dependent activity.

Follicular dendritic cells (FDCs) periodically arrange membrane-bound immune complexes (ICs) of T-dependent Ags 200-500A apart, and in addition to Ag, they provide B cells with costimulatory signals. This prompted the hypothesis that Ag in FDC-ICs can simultaneously cross-link multiple BCRs and induce T cell-independent (TI) B cell activation. TI responses are characterized by rapid IgM production.

Fibroblastic reticular cells of the peripheral lymphoid organs: unique features of a ubiquitous cell type.

The highly ordered structure in peripheral lymphoid tissues is maintained by continuous interactions between their hemopoietic and stromal components. The main reticular cell type, fibroblastic reticular cells (FRCs) emerged as a considerably heterogeneous group of the stroma. These cells have diverse roles beyond architectural scaffolding.

Ultrastructural study of highly enriched follicular dendritic cells reveals their morphology and the periodicity of immune complex binding.

Follicular dendritic cells (FDCs) are immune accessory cells found in the follicles of secondary lymphoid organs where they promote B cell maturation in germinal centers (GCs) that develop following antigen exposure. Recently, we published a method for isolating functional murine FDCs in high purity. We reasoned that disruption of FDC reticula in vivo would alter FDC morphology.

Immune complex-bearing follicular dendritic cells deliver a late antigenic signal that promotes somatic hypermutation.

We reasoned that immune complex (IC)-bearing follicular dendritic cells (FDCs) promote somatic hypermutation (SHM). This hypothesis was tested in murine germinal center reactions induced in vitro by coculturing 6-day (4-hydroxy-3-nitrophenyl) acetyl-primed but unmutated lambda+ B cells, chicken gamma-globulin (CGG) memory T cells, FDCs, and ICs (anti-CGG plus NP-CGG). Mutations in primed lambda+ B cells were obtained only when both FDCs and immunogen were present.

TLR4 on follicular dendritic cells: an activation pathway that promotes accessory activity.

Microbial molecular patterns engage TLRs and activate dendritic cells and other accessory cells. Follicular dendritic cells (FDCs) exist in resting and activated states, but are activated in germinal centers, where they provide accessory function. We reasoned that FDCs might express TLRs and that engagement might activate FDCs by up-regulating molecules important for accessory activity.

Follicular dendritic cells stimulated by collagen type I develop dendrites and networks in vitro.

Follicular dendritic cells (FDCs) reside in germinal centers in which their dendrites interdigitate and form non-mobile networks. FDC purification requires the use of collagenase and selection columns and leaves FDCs without detectable dendrites when examined by light microscopy. We have reasoned that isolated FDCs might reattach to a collagen matrix, extend their processes, and form immobile networks in vitro.

Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development.

Follicular dendritic cell (FDC)-FcgammaRIIB levels are up-regulated 1-3 days after challenge of actively immunized mice with Ag. This kinetics suggested that memory cells are not driving this response, prompting the hypothesis that immune complex (IC)-FDC interactions lead to FDC activation. To test this, mice passively immunized with anti-OVA Ab were OVA challenged to produce IC.

Isolation of functionally active murine follicular dendritic cells.

Biochemical, genetic, and immunological studies of follicular dendritic cells (FDCs) have been hampered by difficulty in obtaining adequate numbers of purified cells in a functional state. To address this obstacle, we enriched FDCs by irradiating mice to destroy most lymphocytes, excised the lymph nodes, and gently digested the nodes with an enzyme cocktail to form single cell suspensions. The FDCs in suspension were selected using the specific mAb FDC-M1 with magnetic cell separation technology.

Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and follicular dendritic cells.

Differences in murine follicular dendritic cells (FDC)-CD23 expression under Th1 vs Th2 conditions prompted the hypothesis that T cells help regulate the phenotype of FDCs. FDCs express CD40, suggesting that T cell-CD40L and lymphokines may be involved in regulating FDC-CD23. To test this, highly enriched FDCs were incubated with CD40L trimer or anti-CD40 to mimic T cell signaling in the presence of IFN-gamma or IL-4.

The influence of immune complex-bearing follicular dendritic cells on the IgM response, Ig class switching, and production of high affinity IgG.

It is believed that Ag in immune complexes (ICs) on follicular dendritic cells (FDCs) selects high affinity B cells and promotes affinity maturation. However, selection has been documented in the absence of readily detectable ICs on FDCs, suggesting that FDC-ICs may not be important. These results prompted experiments to test the hypothesis that IC-bearing murine FDCs can promote high affinity IgG responses by selecting B cells after stimulating naive IgM(+) cells to mature and class switch.

Role of CD44 and its v7 isoform in staphylococcal enterotoxin B-induced toxic shock: CD44 deficiency on hepatic mononuclear cells leads to reduced activation-induced apoptosis that results in increased liver damage.

Exposure to bacterial superantigens such as staphylococcal enterotoxin B (SEB) leads to the induction of toxic shock syndrome which results in multiorgan failure, including liver damage. In the present study, we investigated the role of CD44 in SEB-induced liver injury. Injection of SEB into d-galactosamine-sensitized CD44 wild-type (WT) mice led to a significant increase in CD44 expression on liver T cells, NK cells, and NKT cells.

Immunoarchitecture of distinct reticular fibroblastic domains in the white pulp of mouse spleen.

The development of peripheral lymphoid tissues requires a series of cognate interactions between hemopoietic and stromal cell populations, including reticular fibroblasts, which form the mesenchymal scaffolding of distinct tissue compartments. Here we describe the formation of different fibroblastic domains in the mouse spleen white pulp by using two new rat monoclonal antibodies (MAbs). In the white pulp, MAb IBL-10 labels both T- and B-cell zone reticular elements at various intensities.

Follicular dendritic cells in aging, a "bottle-neck" in the humoral immune response.

Senescence leads to the appearance of atrophic follicular dendritic cells (FDCs) that trap and retain little immune complexes (IC), generate few memory B cells, and induce a reduced number of germinal centers (GC). Deficiencies in antibody responses to T cell dependent exogenous antigens such as pneumonia and influenza vaccines may reflect intrinsic FDC defects or altered FDC-B cell interactions. We recently studied antigen handling capacity and co-stimulatory activity of old FDCs and determined age-related changes in the expression or function of FcgammaRII or CR1 and 2 on FDCs.

FcgammaRII expression on follicular dendritic cells and immunoreceptor tyrosine-based inhibition motif signaling in B cells.

Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif (ITIM) signaling and inhibit B cell activation by coligating B cell receptor for antigen (BCR) and FcgammaRII. Nevertheless, IC on follicular dendritic cells (FDC) stimulate rapid germinal center (GC) B cell proliferation suggesting that interactions between IC and FDC render IC capable of B cell activation. To understand this, we studied the kinetics of FDC FcgammaRII and complement receptors 1 and 2 (CR1&2) expressions during the GC reaction and determined whether FDC FcgammaRII could bind Fc in IC and block ITIM signaling.

Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates with immunoreceptor tyrosine-based inhibition motif signaling in B cells and reduced germinal center formation.

Aging is associated with reduced trapping of Ag in the form of in immune complexes (ICs) by follicular dendritic cells (FDCs). We postulated that this defect was due to altered regulation of IC trapping receptors. The level of FDC-M1, complement receptors 1 and 2, FcgammaRII, and FDC-M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge.

Targeted deletion of CD44v7 exon leads to decreased endothelial cell injury but not tumor cell killing mediated by interleukin-2-activated cytolytic lymphocytes.

In the current study, we investigated the nature and role of CD44 variant isoforms involved in endothelial cell (EC) injury and tumor cell cytotoxicity mediated by IL-2-activated killer (LAK) cells. Treatment of CD44 wild-type lymphocytes with IL-2 led to increased gene expression of CD44 v6 and v7 variant isoforms and to significant induction of vascular leak syndrome (VLS). CD44v6-v7 knockout (KO) and CD44v7 KO mice showed markedly reduced levels of IL-2-induced VLS.

Age-related depression of FDC accessory functions and CD21 ligand-mediated repair of co-stimulation.

Morphological and kinetic studies of immune complex (IC) trapping by follicular dendritic cells (FDC) show marked age-related deficits. We postulated that a reduction in trapped IC, which generate CD21 ligands (L) on FDC, would lead to inadequate FDC-Ag-B cell interactions resulting in depressed Ab responses. To determine whether the age-related defect was the result of the aging of FDC or changes in the in vivo microenvironment of FDC (i.

Appearance and phenotype of murine follicular dendritic cells expressing VCAM-1.

The architecture of lymphoid follicles is determined by a series of interactions between lymphoid and follicular stromal cells. A cardinal population in the non-lymphoid compartment is the follicular dendritic cell (FDC), whose communication with resting and activated B cells involves various adhesive interactions. The FDC phenotype variably includes the display of vascular cell adhesion molecule (VCAM-1).