New study identifies genes linked to high production of key antibody immunoglobulin G

Good news! Impressive work!

"Key takeaways

1. Researchers studying white blood cells identified an atlas of genes linked to high production and release of the most common type of antibody found in the human body, known as immunoglobulin G.
2. The finding could be a step toward new antibody-based treatments and improvements in the effectiveness of cell therapies.
3. The researchers used microscopic containers called nanovials, which were developed at UCLA, to capture the individual cells they studied.

... Scientists have known for decades that a population of white blood cells, called plasma B cells, make IgG. Plasma B cells are highly efficient, producing more than 10,000 IgG molecules every second. But the molecular mechanisms that enable plasma cells to secrete antibodies into the bloodstream are still not fully understood. ...

Their analysis found that genes involved with producing energy and eliminating abnormal proteins were even more important for high IgG secretion than the genes containing instructions for making the antibody itself. They also discovered that the presence of CD59, a gene that had not previously been linked to IgG secretion, is a better predictor of high-producing plasma cells than other genetic markers already associated with this cell type. ...

For instance, knowing which genes are associated with higher secretion of an antibody could be used by pharmaceutical makers to engineer cells that secrete large volumes of the antibody. That knowledge could also be applied to an emerging strategy that introduces engineered cells directly to patients’ bodies, such as the potential cell therapies under development by University of Washington immunologist Richard James, a co-corresponding author of the paper. ..."

From the abstract:

"The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human B cells and link this information to surface markers and transcriptomes from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborate the association between IgG secretion and CD38/CD138. By using oligonucleotide-labeled antibodies we find that upregulation of pathways for protein localization to the endoplasmic reticulum and mitochondrial oxidative phosphorylation are most associated with high IgG secretion, and uncover surrogate plasma cell surface markers (e.g., CD59) defined by the ability to secrete IgG. Altogether, this method links quantity of secretion with single-cell sequencing (SEC-seq) and enables researchers to fully explore the links between genome and function, laying the foundation for discoveries in immunology, stem cell biology, and beyond."

New study identifies genes linked to high production of key antibody | UCLA Discovery made possible by UCLA-developed nanotechnology

SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells (open access)

Fig. 1: Workflow to link IgG secretion to surface markers and transcriptomes at the single-cell level.

Fig. 2: Linking IgG secretion to cell surface markers and intracellular machinery using flow cytometry.