Effect of Antigen Valency on Autoreactive B-Cell Targeting.

Many autoimmune diseases are characterized by B cells that mistakenly recognize autoantigens and produce antibodies toward self-proteins. Current therapies aim to suppress the immune system, which is associated with adverse effects. An attractive and more specific approach is to target the autoreactive B cells selectively through their unique B-cell receptor (BCR) using an autoantigen coupled to an effector molecule able to modulate the B-cell activity.

Integrated Single-Cell (Phospho-)Protein and RNA Detection Uncovers Phenotypic Characteristics and Active Signal Transduction of Human Antibody-Secreting Cells.

Single-cell technologies are currently widely applied to obtain a deeper understanding of the phenotype of single-cells in heterogenous mixtures. However, integrated multilayer approaches including simultaneous detection of mRNA, protein expression, and intracellular phospho-proteins are still challenging. Here, we combined an adapted method to in vitro-differentiate peripheral B-cells into antibody-secreting cells (ASCs) (i.

Single-cell intracellular epitope and transcript detection reveals signal transduction dynamics.

To further our understanding of how biochemical information flows through cells upon external stimulation, we require single-cell multi-omics methods that concurrently map changes in (phospho)protein levels across signaling networks and the associated gene expression profiles. Here, we present quantification of RNA and intracellular epitopes by sequencing (QuRIE-seq), a droplet-based platform for single-cell RNA and intra- and extracellular (phospho)protein quantification through sequencing. We applied QuRIE-seq to quantify cell-state changes at both the signaling and the transcriptome level after 2-, 4-, 6-, 60-, and 180-min stimulation of the B cell receptor pathway in Burkitt lymphoma cells.