It is such fantastic work Lauren! Congrats.

It seems these sugar-specific B cells don’t follow some of the “rules” for selection, which could in theory mean differences for tolerance checkpoints too!

Many anti-sugar Abs are unmutated IgM’s, including those that recognise host-glycans. So this may be a restricted phenomenon.

That’s an interesting question, particularly as the Strep A glycan has also been implicated as an autoantibody involved in rheumatic fever.

Right now, it’s still unclear.

Congrats to first authors @hollyfryer.bsky.social and Cathy Pitt, and all my co-authors many of whom provided the amazing clinical samples that powered this research.

@joshosowicki.bsky.social @njmoreland.bsky.social @melanieneeland.bsky.social (and many more not on 🦋)

These findings reveal how age and infection history can influence the quality, quantity, and isotype use of sugar-specific B cells. This work has important implications for the design and schedule of glycan-containing vaccines.

We conclude that mucosal pathogen encounters elicit glycan
responses that class-switch, evolve and diversify through the GC.

📖🥊 take that textbook!

We found that Strep A infection induced sugar B cells to enter the Germinal centre where they became highly mutated.

How were they doing this? By comparing to protein responses (SpyCEP) we found that sugar B cells had a molecular signature consistent with receiving reduced T cell help.

By studying human blood, spleen and tonsils, including samples from a Strep A human challenge model, we show that sugar B cell responses shift from IgM
towards IgG and IgA memory with age and antigen exposure.

We asked - is this dogma correct when sugar-specific B cells could engulf whole bacteria? (that contain proteins for T cells to recognise).

We focussed on Strep A, where the sugar (GAC) is a leading glycoconjugate vaccine candidate.

Image: Natalia Korotkova

As T cells can’t “see” sugar molecules via their T cell receptor, text books say that antibodies to sugars occur without T cell help. T cell help is critical for germinal centres (GC), the structure in which the antibody sequence on B cells gets mutated with the aim of increasing binding strength.

I would love to see this 📖 one day!

8/9 In short, we suggest in vitro stimulation activates ag-specific T cells, which secrete cytokines and activate Treg and Th17/22 cells. Without careful phenotyping, all of these cells can get picked up as AIM+, accounting for the Th17-like memory cells found in many virus-specific AIM datasets.

This is phenomenal!! What a creative bunch!

I’m loving these! Keep them coming!

Thanks Tri!

@rhcmcg.bsky.social my fantastic co-author Reuben McGregor from University of Auckland is on 🦋 too!