The latest paper from our lab is out now in Nature Communications!

In “Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue”, co-authored by myself and Lucia Montorsi along with our collaborators, we used a combination of spatial transcriptomics and multiplexed single-cell technologies to pinpoint the DN2 B cells, known to be enriched in the blood in patients with lupus, as being present in healthy gut. When in the gut, these DN2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q, adjacent to bacteria.

The normal functions of DN2 B cells, DNASE1L3 and C1q in the gut are likely to relate to bacterial recognition, bacterial killing and disposal of bacterial debris including DNA. Failure of such a system could result in persistence of bacterial DNA that may stimulate an autoimmune response.

Read it here: https://www.nature.com/articles/s41467-024-48267-4

Our new preprint is live on bioRxiv! We identify a link between microbiota, intestinal immunity and autoimmunity using protocols that include a new method to resolve spatial transcriptomics to single cells

Read here: https://www.biorxiv.org/content/10.1101/2023.08.29.555265v1

The latest publication from our lab, “Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood“, is out now in Science Immunology!

Led by Dr Jacqueline Siu and supervised by Prof Jo Spencer and Dr Gavin Pettigrew, we use analysis of gut-associated lymphoid tissue, mesenteric lymph node, and spleen tissues from diseased human transplant donors to show that CD27⁺IgM⁺ unswitched B cells differed mostly between tissues. We identified two distinct MZ populations were identified among the cells, which differed in their expression levels of BAFFR, CD24, CCR7, and CD27. RNA-Seq data from the tissues also identified two MZ-like B cell populations with similar characteristics, and also revealed that MZB-1 showed higher mutation levels than MZB-2 cells. RNA-Seq was also used to compare blood B cells from lupus patients and healthy donors, which again clustered MZ-like B cells into two populations that differed in mutation frequency in their V regions. SLE patients lacked MZB-1 cells and this was confirmed by flow cytometry.

Read the paper here.

The Spencer lab has collaborated on two new papers which have come out recently:

A SIMPLI (Single-cell Identification from MultiPLexed Images) approach for spatially resolved tissue phenotyping at single-cell resolution: A software pipeline, named SIMPLI, for end-to-end analysis of Imaging Mass Cytometry data (software can be found here). Led by Michele Bortolomeazzi, a collaboration with the Ciccarelli lab at Crick.

Disrupted Peyer’s patch microanatomy in COVID-19 including germinal centre atrophy independent of local virus: Covid-19 infection disrupts the Peyer’s patch of the GI tract, regardless of the levels of virus in that location, suggesting the virus impacts the body’s ability to mount an effective intestinal immune response. Led by Silvia Cellone Trevelin, a collaboration with the Neil lab at KCL.

Read the article here: https://www.biorxiv.org/content/10.1101/2021.12.17.473179v1

A new pre-print from our lab in collaboration with the Neil lab at KCL has gone live today. In it, analysis of post-mortem tissues from the gastrointestinal tract of patients who died with COVID-19 showed that virus was present in epithelium and lamina propria macrophages, but not in lymphoid tissues of patients who had PCR-confirmed infection of the GI tract. Germinal centres were disrupted, as were the delineation of B cell and T cell zones, leading to reduced potential for B- and T-cell interaction. These observations suggest the ability to mount an intestinal immune response to COVID-19 is compromised.