Journal Article Preprint Epublish 1 citation
PubMed: 40236127 DOI: 10.1101/2025.03.26.645614
Antibody responses against bacterial glycans affinity mature and diversify in germinal centers.
bioRxiv
Authors: Holly A Fryer, Catherine Pitt, Hannah R Frost, Nitika Kandhari, Sean Byars, Pailene S Lim, Trang T Nguyen, Kaneka Chheng, Natalie Caltabiano, Alana L Whitcombe, Julianne Hamelink, Dean Andrew, Gareth Lloyd, Brian Wilson-Boyd, Nicola Slee, Jodie Ballantine, Sarju Vasani, Kathryn Girling, Liam Gubbels, Eric Levi, Karen Davies, Stuart Tangye, Jonathan Noonan, Nicole J Moreland, Isaak Quast, Marcus J Robinson, Stephen W Scally, Melanie Neeland, Shivanthan Shanthikumar, Joshua Osowicki, David M Tarlinton, Andrew C Steer, Michelle J Boyle, Danika L Hill
Abstract
Anti-carbohydrate antibodies (Abs) play crucial roles in pathogen control, but their generation remains poorly understood. By studying responses to in humans, we reveal that the glycan-targeted response shifts from IgM towards IgG and IgA memory with age and antigen exposure across blood, spleen, and tonsils. Both natural colonization and controlled human infection with increased class-switched B cells, with evidence of within-clone switching. Glycan-specific B cells readily participated in germinal center (GC) responses and showed robust somatic hypermutation despite a molecular signature consistent with receiving reduced T cell help. We conclude that mucosal pathogen encounters elicit glycan responses that class-switch, evolve and diversify through the GC. These findings reveal how age and infection history can influence the quality, quantity, and isotype use of glycan-specific B cells, with implications for the design and schedule of glycan-containing vaccines.
MeSH
Cells, Antibody Formation, Polysaccharides, Germinal Center, Infections