I am very excited to share the final story of my PhD, online now as a pre-print in @biorxivpreprint, where we dissect the opposing effects of antibody-feedback and memory T cell help on recall germinal centers (GCs). 1/n https://t.co/sKiEUOYiiT

Congratulations @victora_lab!

Huge honor and pleasure to be with @RockefellerUniv grads and faculty. A jewel of an institution, and some mighty students. Go forth and make #science for people and the planet.

Lastly, I am very grateful for the support of my mentors Gabriel (@victora_lab) and @LukaMesin throughout my PhD, as well as for instrumental help from co-authors @MarijevtWout and @hobbs_alvaro. 12/end

All in all, a nice example of the immune system using antibody-mediated feedback to guide secondary responses exactly to where they are needed. 11/n

Meaning that recall GCs are most useful for variant boosting, where Ab feedback can direct B cells specifically to “holes” in coverage left by escape mutations, promoting Abs precisely to these all-important escape epitopes. Ultimately, this would result in reduced OAS. 10/n

We propose a model in which the fundamental role of recall GCs, enforced by antibody-mediated feedback, is to mature naïve-derived B cells specifically tailored to escape epitopes on variant antigens. 9/n

Hapten-carrier experiments show that excess help from memory T cells is what allows B cells with undetectable antigen binding to form GCs in the homologous setting. Without such excess help, antibody feedback completely prevents the formation of secondary GCs. 8/n

(as prescribed in previous work from @ian_cockburn (PMID 32697938), Facundo Batista (PMID 35987201), and @NussenzweigL) 7/n https://t.co/T49ls6Chot

Antigen binding by secondary GC B cells was restored partly when mice were boosted with viral variant strains, and almost entirely when we depleted primary antibody secreting cells; i.e., feedback from primary Ab prevents GC entry by B cells with overlapping specificities. 6/n

Here, we show that this drastic split between the cellular and serum compartments is at least partly explained by a marked decrease in the ability of recall GC B cells to detectably bind antigen, so that any Ab that they secrete cannot contribute to antigen-specific titers. 5/n

Second, using mice in which the antibodies themselves could be fate-mapped, we found that serum antibodies consistently derive from the cohort of B cells engaged during the primary response, even upon repeated boosting with the same antigen. 4/n https://t.co/fpHcoJbYdh

First, together with @LukaMesin, we used GC B cell fate-mapping to show that recall GCs engage mostly B cells with no prior GC experience and thus have the potential to induce de novo antibodies. 3/n https://t.co/cJJKOFwK4J

This story originated from an effort to explain the findings of two of our recent studies that at face value could appear contradictory, regarding the use of memory versus de novo induced B cells for recall antibody responses in relation to “original antigenic sin” (OAS). 2/n

Meet @Arien_Schiepers: award-winning UU alum (bio-med)! 🎓 His groundbreaking PhD research won him the International #BirnstielAward for Doctoral Studies in Molecular Life Sciences 2023 (@IMPvienna). Ariën, congratulations on your extraordinary achievements! 🎉 #proudUUAlum

Thank you very much @StearnsLab, and the entire @RockefellerUniv Dean's office, for the award nomination and your support throughout my PhD!

Very happy and honored to be selected for the Birnstiel Award! I’m extremely grateful for the support of my mentors Gabriel (@victora_lab) and @LukaMesin at @RockefellerUniv. Thank you to @IMPvienna for this honor, and congratulations to my fellow awardees!

At AAI, just listened to a fantastic talk by @Arien_Schiepers, very elegant new mouse model to understand B cell recruitment to the GC and the original antigenic sin. https://t.co/JGHxMOlwvO @victora_lab #AAI2023 #immunology2023