This work would have been impossible without my amazing co-authors @ursulaschoeberl.bsky.social and Johanna Fitz or without the insightful supervision of Rushad Pavri. This work was supported by @impvienna.bsky.social and many fantastic collaborators. (Fin)

Take-home message: Antibody maturation is made possible through a dynamic, multiway chromatin hub that can be maintained without cohesin, and where SHM and CSR coexist. (9/10)

And most intriguingly: CSR activation didn’t disrupt SHM. The V region kept interacting with enhancers, and SHM & transcription remained stable. So CSR and SHM can occur not competitively, but cooperatively. (8/10)

Further, the new loops also did not decrease V-region transcription or SHM. This is super interesting, because it suggests that CSR and SHM are not competitive - a question that has been discussed for a long time. (7/10)

When we activated an IGH switch region (γ1), it was recruited into the hub. This is essential for CSR. Even without cohesin, this recruitment still occurred. So: loop extrusion isn’t required for enhancer-promoter contact or switch region activation. (6/10)

Using Tri-C, which maps multiway DNA contacts, we mapped the 3D folding of the human IGH locus during SHM. We discovered a multiway chromatin hub: The V region simultaneously contacts all its major enhancers, clustering them into one regulatory hub. (4/10)

Here’s the twist: Cohesin depletion did not disrupt active transcription or the hub structure. This suggests other mechanisms are sufficient to maintain the hub. (5/10)

But how are these processes organized in 3D at the complex human IGH locus? How are these structures formed and maintained? Does it require loop extrusion via cohesin? Can SHM and CSR coexist, or do they compete for access? We wanted answers. (3/10)

Background: SHM introduces mutations into the V region of the IGH locus, fine-tuning antibodies for higher affinity towards antigens. CSR lets B cells change antibody isotypes (classes) and redirect immune signaling. (2/10)

New Paper!
How do human B cells use dynamic DNA topology during antibody maturation? Our research published in Molecular Cell reveals how somatic hypermutation (SHM) and class switch recombination (CSR) work in the context of a regulated multiway 3D chromatin hub. (1/10) 🧵

➡️Read our interview with the authors: imp.ac.at/news/article/how-do-human-antibodies-get-better-at-fighting-infections

Our Pavri Lab shows in a new study how B cells organize their DNA during somatic hypermutation, a key step for making protective antibodies after infection or vaccination.

➡️Read the paper: doi.org/10.1016&j.molcel.2025.06.003

arrived at bsky!