Partial block in B lymphocyte development at the transition into the pre-B cell receptor stage in Vpre-B1-deficient mice

The surrogate light chain (SL) is composed of two polypeptides, Vpre-B and λ5. In large pre-BII cells the SL chain associates with Ig μ heavy chain (μH) to form the pre-B cell receptor (pre-BCR). In mice there are two Vpre-B genes which are 98% identical within the coding regions. The two genes are co-expressed at the RNA level and encode functional proteins that can assemble with λ5. However, it is not known whether both gene products serve the same function in vivo. Here we have established mice that lack the Vpre-B1 gene (VpreB1-/-), but still express the Vpre-B2 gene, both as RNA and protein. In Vpre-B1-/- mice, the bone marrow cellularity and the percentage of B220+ cells is normal. However, among the B220+ cells, the percentage of pre-BI cells is increased, and the percentage of pre-BII and immature B cells is slightly decreased, suggesting that the lack of Vpre-B1 causes a partial block at the transition from pre-BI to pre-BII cells, i.e. into the pre-BCR stage. The number of cells that produce a functional pre-BCR is thus lower, but the cells that reach this stage are normal as they can be expanded by proliferation and then differentiate into more mature cells. The spleens of Vpre-B1 homozygous mutant mice show normal numbers of B and T lymphocytes. Moreover, the Ig loci are allelicly excluded and the homozygous mutant mice respond with normal levels of antigen-specific antibodies to T-dependent antigens. These results demonstrate that Vpre-B2 alone is capable of supporting B lymphocyte development in the bone marrow and can give rise to immuno-competent cells in the peripher

Staying Normal under Abnormal Circumstances: Publishing during a Global Pandemic

An introduction to volume 8, issue 2 of Teaching & Learning Inquiry

Water contamination of urban areas by pharmaceuticals

The occurrence and fate data of pharmaceuticals in the environment were described in the article. The main list of pharmaceuticals groups identified in surface and sewage waters was shown according to studies of laboratories in the U.S. and Europe. The main approaches for reduction of pharmaceuticals releasing into environment and monitoring of surface water were considered

CD21-/low B cells: a snapshot of a unique B cell subset in health and disease

B cells represent one of the cellular components of the immune system thatprotects the individual from invading pathogens. In response to the invader,these cells differentiate into plasma cells and produce large amounts of antibodiesthat bind to and eliminate the pathogen. A hallmark of autoimmune diseases isthe production of autoantibodies i.e. antibodies that recognize self. Those that areconsidered pathogenic can damage tissues and organs, either by direct binding orwhen deposited as immune complexes. For decades, B cells have been consideredto play a major role in autoimmune diseases by antibody production. However, aspathogenic autoantibodies appear to derive mainly from T cell dependentresponses, T cells have been the focus for many years. The successful treatment ofpatients with autoimmune diseases with either B cell depletion therapy(rituximab) or inhibition of B cell survival (belimumab), suggested that notonly the autoantibodies but also other B cell features are important. This hascaused a surg e of interest in B cells and their biology resulting in theidentification of various subsets e.g. regulatory B cells, several memory B cellsubsets etc. Also, in other conditions such as chronic viral infect ions and primaryimmunodeficiency, several B cell subsets with unique characteristics have beenidentified. In this review, we will discuss one of these subsets, a subset that isexpanded in conditions characterized by chronic immune stimulation. This B cellsubset lacks, or expresses low, surface levels of the complement receptor 2(CD21) and has therefore been termed CD21-/lowB cell

Resonant Auger spectroscopy at the L2,3 shake-up thresholds as a probe of electron correlation effects in nickel

The excitation energy dependence of the three-hole satellites in the L3-M4,5M4,5 and L2-M4,5M4,5 Auger spectra of nickel metal has been measured using synchrotron radiation. The satellite behavior in the non-radiative emission spectra at the L3 and L2 thresholds is compared and the influence of the Coster-Kronig channel explored. The three-hole satellite intensity at the L3 Auger emission line reveals a peak structure at 5 eV above the L3 threshold attributed to resonant processes at the 2p53d9 shake-up threshold. This is discussed in connection with the 6-eV feature in the x-ray absorption spectrum.Comment: 8 pages, 4 figures; http://prb.aps.org/abstract/PRB/v58/i7/p3677_

Intramolecular vibronic dynamics in molecular solids: C60

Vibronic coupling in solid C60 has been investigated with a combination of resonant photoemission spectroscopy (RPES) and resonant inelastic x-ray scattering (RIXS). Excitation as a function of energy within the lowest unoccupied molecular orbital resonance yielded strong oscillations in intensity and dispersion in RPES, and a strong inelastic component in RIXS. Reconciling these two observations establishes that vibronic coupling in this core hole excitation leads to predominantly inelastic scattering and localization of the excited vibrations on the molecule on a femtosecond time scale. The coupling extends throughout the widths of the frontier valence bands.

Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy–Focus on FcγRIIB

Immunotherapy with therapeutic antibodies has increased survival for patients with hematologic and solid cancers. Still, a significant fraction of patients fails to respond to therapy or acquire resistance. Understanding and overcoming mechanisms of resistance to antibody drugs, and in particular those common to antibody drugs as a class, is therefore highly warranted and holds promise to improve response rates, duration of response and potentially overall survival. Activating and inhibitory Fc gamma receptors (FcγR) are known to coordinately regulate therapeutic activity of tumor direct-targeting antibodies. Similar, but also divergent, roles for FcγRs in controlling efficacy of immune modulatory antibodies e.g., checkpoint inhibitors have been indicated from mouse studies, and were recently implicated in contributing to efficacy in the human clinical setting. Here we discuss evidence and mechanisms by which Fc gamma receptors–the “antibody checkpoints”–regulate antibody-induced antitumor immunity. We further discuss how targeted blockade of the sole known inhibitory antibody checkpoint FcγRIIB may help overcome resistance and boost activity of clinically validated and emerging antibodies in cancer immunotherapy

Fiber-Flux Diffusion Density for White Matter Tracts Analysis: Application to Mild Anomalies Localization in Contact Sports Players

We present the concept of fiber-flux density for locally quantifying white matter (WM) fiber bundles. By combining scalar diffusivity measures (e.g., fractional anisotropy) with fiber-flux measurements, we define new local descriptors called Fiber-Flux Diffusion Density (FFDD) vectors. Applying each descriptor throughout fiber bundles allows along-tract coupling of a specific diffusion measure with geometrical properties, such as fiber orientation and coherence. A key step in the proposed framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tract-profiles enable meaningful inter-subject comparisons and group-wise statistical analysis. We demonstrate our method using two different datasets of contact sports players. Along-tract pairwise comparison as well as group-wise analysis, with respect to non-player healthy controls, reveal significant and spatially-consistent FFDD anomalies. Comparing our method with along-tract FA analysis shows improved sensitivity to subtle structural anomalies in football players over standard FA measurements