This work was co-led by my wife, Marla Glass! Thanks to everyone who contributed to this work, including my PI @evnewell.bsky.social, and our institutes, the @alleninstitute.org and the @fredhutch.org!
Posts by David R. Glass, PhD
All the data and code are available now and we have an amazing visualization tool to explore our CITEseq data! We also relate a low-dimensional gating strategy for sorting and clinical immune monitoring. apps.allenimmunology.org/aifi/resourc...
We also looked for our subsets in patient recovering from myeloma in the months and years after induction therapy and autotransplant. We found that the most mature ASCr subsets failed to recover to healthy levels even two years after transplant demonstrating longterm humoral defects.
Multiple donors had immature HLA-DR+ cycling ASCp cells specific to smallpox vaccine antigens, decades after vaccination. This suggests a mechanism by which bystander-activated memory B cells can differentiate into ASCs in the absence of antigen to supplement long-lived humoral immunity!
To find long-lived subsets, we evaluated specificity to childhood vaccine antigens in older adults. All three resident ASCr subsets, including CD19+ and CD19- cells were long-lived and were specific to measles and smallpox vaccine antigens. But we also had a really unexpected finding!
We performed spatial proteomics on bone marrow cores and found that ASC subsets preferred residing in niches with ASCs with the same phenotype, suggesting these niches attract particular subsets or enforce subset identities.
This coincided with a reduction in antibody secretion in mature ASCr subsets when compared to more immature peripheral ASC (ASCp) subsets found in both blood and marrow.
We performed volumetric imaging and found resident ASC subsets (ASCr; found exclusively in the bone marrow) generated large, efficient mitochondrial networks while simultaneously reducing overall endoplasmic reticulum volume.
Our new preprint deeply profiling human antibody-secreting cells (ASCs) is out! We used single-cell multi-omics to discover 5 subsets and relate their surface protein profiles gene expression profiles and epigenetic regulatory programs. And that's just the start! www.biorxiv.org/content/10.6...
Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity www.biorxiv.org/content/10.64898/2026.04...
A study from the lab of @evnewell.bsky.social looks at the immune response to multiple myeloma. It turned out the most interesting thing was what they didn’t find: T cells that had already recognized and tried to fight off tumor cells. Read more: pubmed.ncbi.nlm.nih.gov/40163891/
I'm happy to share our new publication exploring T cell responses in patients with newly diagnosed multiple myeloma. Using single-cell multi-omics, we found no evidence of T cell exhaustion nor a productive clonal T cell response, suggesting myeloma uses an alternative immune evasion strategy.
Come hear about human antibody-secreting cell multi-omic profiles and functional characteristics at my talk in the Lymphocyte Homeostasis session Tuesday @ 12:30 in Room 320! #AAI2025 @aai.org
I'm also happy to receive the AAI-Thermo Fisher Trainee Achievement Award! This will be my first AAI Meeting, so I'm thrilled to be introduced to the community with such a nice welcome!
I'm presenting my research investigating multi-omic profiles and functional characteristics of human antibody-secreting cells at the Lymphocyte Homeostasis Block Symposium Tuesday at 12:30. If you love high-dimensional analyses, human immunology, and good old-fashioned benchtop experiments, stop by!