Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

Human Bone Marrow Plasma Cell Atlas: Maturation and Survival Pathways Unraveled by Single Cell Analyses.

Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4.

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection.

Background: SARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses.

Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein.

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein.

Understanding and measuring human B-cell tolerance and its breakdown in autoimmune disease.

The maintenance of immunological tolerance of B lymphocytes is a complex and critical process that must be implemented as to avoid the detrimental development of autoreactivity and possible autoimmunity. Murine models have been invaluable to elucidate many of the key components in B-cell tolerance; however, translation to human homeostatic and pathogenic immune states can be difficult to assess. Functional autoreactive, flow cytometric, and single-cell cloning assays have proven to be critical in deciphering breaks in B-cell tolerance within autoimmunity; however, newer approaches to assess human B-cell tolerance may prove to be vital in the further exploration of underlying tolerance defects.

The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months.

Epigenetic programming underpins B cell dysfunction in human SLE.

Systemic lupus erythematosus (SLE) is characterized by the expansion of extrafollicular pathogenic B cells derived from newly activated naive cells. Although these cells express distinct markers, their epigenetic architecture and how it contributes to SLE remain poorly understood. To address this, we determined the DNA methylomes, chromatin accessibility profiles and transcriptomes from five human B cell subsets, including a newly defined effector B cell subset, from subjects with SLE and healthy controls.

Efficient micro-cavity top emission OLED with optimized Mg:Ag ratio cathode.

Micro-cavity top-emitting organic light emitting diodes (TEOLEDs) are now receiving prominence as a technology for the active matrix display applications. The semi-transparent metal cathode plays the crucial role in realizing TEOLEDs structure. Here, we report the optimization results on Mg:Ag ratio as the semitransparent cathode deposited by vacuum thermal evaporation.

Successful Thoracic Duct Ligation for Plastic Bronchitis in an Adult.

Plastic bronchitis is a rare and potentially life-threatening disease characterized by the development of obstructive fibrinous tracheobronchial casts and hypoxic respiratory failure. With its poorly understood cause and rare occurrence in the adult population, few treatment strategies have been described in adults with this condition. In this report, we present a case of successful treatment of an adult with plastic bronchitis, using thoracic duct ligation and resulting in full resolution of airway cast development.

Macroscopic alignment of chromonic liquid crystals using patterned substrates.

We demonstrate an efficient technique to align lyotropic chromonic liquid crystals (LCLCs) using secondary sputtering lithography (SSL). Monodomains of LCLCs prepared using SSL maintained their stable alignment for days. A generalization of Berreman's theory was employed to determine the anchoring strength of LCLCs on tessellated surface patterns.

Fabrication of sub-20 nm nano-gap structures through the elastomeric nano-stamp assisted secondary sputtering phenomenon.

We describe a highly efficient method for fabricating controllable and reliable sub-20 nm scale nano-gap structures through an elastomeric nano-stamp with an embedded ultra-thin pattern. The stamp consists of ultrahigh resolution (approximately 10 nm) and high aspect ratio (ca. 15) metal nano-structures, which are obtained by secondary sputtering lithography (SSL).

Fabrication of complex 3-dimensional patterned structures on a ∼10 nm scale from a single master pattern by secondary sputtering lithography.

We describe a highly efficient method for fabricating a variety of complex 3D nano-patterns from a single master pattern using secondary sputtering lithography, which is a 10 nm scale patterning method that we have developed. A rapid etching rate in the bottom part of the PS pillar during the RIE process can produce various nanostructure shapes and the PS residual layer thickness can influence various feature dimensions, due to the controlled RIE time leading to different PS layer thicknesses. This technique provides a highly effective method for producing various complex 3D patterns from a single master pattern.

Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data.

Background: Advances in multiparameter flow cytometry (FCM) now allow for the independent detection of larger numbers of fluorochromes on individual cells, generating data with increasingly higher dimensionality. The increased complexity of these data has made it difficult to identify cell populations from high-dimensional FCM data using traditional manual gating strategies based on single-color or two-color displays.

Methods: To address this challenge, we developed a novel program, FLOCK (FLOw Clustering without K), that uses a density-based clustering approach to algorithmically identify biologically relevant cell populations from multiple samples in an unbiased fashion, thereby eliminating operator-dependent variability.

A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus.

Human memory B cells comprise isotype-switched and nonswitched cells with both subsets displaying somatic hypermutation. In addition to somatic hypermutation, CD27 expression has also been considered a universal memory B cell marker. We describe a new population of memory B cells containing isotype-switched (IgG and IgA) and IgM-only cells and lacking expression of CD27 and IgD.