labphan.bsky.social
B cells | Macrophages | Immunity | Autoimmunity | Cancer | Osteoclasts | Osteomorphs | Intravital imaging | Precision Immunology
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Thanks Kamila!
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Not sure if this is what you meant. DOCK8 deficiency (but not STAT3) is reported to have peripheral blood ILC3 defect which corrects after HSCT. In contrast, SCID patients may not reconstitute their NKs and ILCs after HSCT with no obvious health consequences suggesting they are dispensable.
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Thanks Mauro! They make beautiful memories!
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Thanks Cheri!
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Thanks Jen!
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So location does matter & boosting on the same side may make a difference! Basic research can underpin clinical translation. Can't have one without the other! Thankful to all our funders especially NHMRC, ACRF & UNSW Scientia Program. Thank you for reading please check out our paper! End 🧵
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This was associated with more rapid secretion of neutralising antibodies against the ancestral strain in the vaccine as well as Delta and Omicron variants. In agreement, there was more somatic hypermutation & antibody diversification in the boosted dLN compared to ndLN.
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Please note caveats about persistent GCs from the COVID mRNA vaccine (Turner, Ellebedy et al. Nature 2021). Regardless, we did see more GCs in the boosted dLN compared to ndLN
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This was all done in inbred genetically modified mice using intravital microscopy. Could boosting the same versus opposite side make a difference in 'wildtype' 'outbred' humans? This is where the Kirby Institute team came into their own! In the clinical study they also sampled the LN by FNB!
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What about the SSMs? To test if vaccine had 'primed' the dLN SSMs we synchronously immunised the ndLN with an irrelevant non-cognate antigen. Now when we boost the 'ndLN' with cognate antigen there was larger recall & more GCs, just like dLN! This effect was abolished by anti-CSF1R mAb blocking.
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Rama did scRNAseq & showed that dLN Bmems were distinct from ndLN Bmems. Upregulated dLN genes were involved in cell adhesion, migration & localisation, BCR activation & GC formation. Upregulated ndLN genes were involved in cell migration, tissue residence & plasma cell vs GC differentiation.
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Is this relative positioning of Bmems in relation to the SCS niche important? Boosting of the dLN led to bigger and better Ab responses with more GCs & affinity maturation compared ndLN. But when SSMs are depleted with anti-CSF1R this effect is abolished.
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Rama used intravital microscopy to show that Bmems were positioned deeper in follicle ndLN vs dLN where they were largely confined to the SCS layer. Depletion of CD169+ SCS macrophages (SSMs) with blocking anti-CSF1R mAb led to relocalisation of dLN Bmems deeper in the follicle.
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We previously showed Bmems reside in a subcapsular sinus (SCS) niche in the draining lymph node (dLN). Antigen recall led to re-entry into 2ËšGCs or plasma cell differentiation in subcapsular proliferative foci (SPF). But what about the non-draining lymph node (ndLN)?
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Welcome!
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Ain't it just? 😊
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Sorry it was my Blue Period.
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Clean the immersion oil from the lens!
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😅
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Strong LZ GC B cell vibes!