ACERTA PHARMA case study
Characterization of antibody secreting cells
Partnership
Acerta Pharma, now part of AstraZeneca, is a Netherlands-based biotech company that developed cancer treatments, particularly for blood cancers like leukemia. Acerta operates as AstraZeneca’s hematology R&D unit.
Key findings
Problem: Understand biochemical differences between antibody secreting cells
Result: IgM and IgA phenotypes show tonic BCR signalling, IgG shows mTOR activity
Scientific impact: First in-depth characterization of the ACS; cells respond in completely different ways to the same drug molecules which can have direct implications in precision treatment
Outcomes
Antibody-secreting cells (ASCs), which produce IgM, IgA, or IgG antibodies, are crucial to humoral immunity. While it is known that different Ig-secreting subclasses exhibit distinct gene expression profiles, a more detailed understanding of the transcriptional and signaling pathways in these cells is needed to better understand their roles in health and disease. By using a method to differentiate peripheral B-cells into ASCs in vitro, we were able to quantify subclass-specific surface markers, transcriptional profiles, and signaling pathway components.
Our approach revealed differential expression of plasmablast and plasma cell markers, as well as TNF-receptor family members, across the Ig subclasses. We also detected the expression of homing receptors corresponding to the specific in vivo niches of IgM, IgA, and IgG ASCs. Demonstrating the potential of our method, we mapped variations in B-cell receptor, IL-2, IL-6, JAK/STAT, and mTOR signaling pathways among IgM, IgA, and IgG ASCs. This strategy is expected to advance our understanding of ASCs in both healthy and diseased states, providing a valuable tool for identifying novel biomarkers and potential drug targets.