Peckham, Hannah;
Radziszewska, Anna;
Robinson, George;
Martin, Lucia;
De Gruijter, Nina M;
Butler, Gary;
Jury, Elizabeth;
... Ciurtin, Coziana; + view all
(2022)
Differential impact of sex steroid hormones on B cell class switching, dependant upon sex chromosomal complement.
Presented at: Division of Medicine Research Retreat 2022, London, UK.
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Abstract
Cis-gender females mount stronger humoral immune responses than cis-gender males in response to infection/vaccination, but are more likely to develop B-cell-driven autoimmune disorders. Murine work suggests a complex interplay between sex chromosomes and hormones creates this sex-bias. Oestrogen has been shown to enhance class-switch recombination(CSR)- the process by which B-cells ‘switch’ to IgG/A/E immunoglobulin isotypes. This study utilises a unique in vivo human model, with samples from both cis-gender and trans-gender age-matched young healthy volunteers, to investigate the impact of sex-chromosomal complement and hormonal milieu on CSR. Peripheral blood samples were collected from cis-male(n=43) and -female(n=62) volunteers(14-31yrs), and trans-male(n=25) and trans-female(n=23) volunteers(15-19yrs) on GnRH-analogue(“puberty blockers”), +/- testosterone or oestrogen treatment, respectively. PBMC/serum phenotyping was performed using flow cytometry and LEGENDplex™ immunoassay. Sorted CD19+ cells from a representative subset(n=22) were sent for RNAseq analysis. Post-pubertal cis-males had lower percentages of class-switched(IgD-CD27+) B-cells than cis-females(p=0.002), specifically pertaining to decreased IgG+ B-cells(p=0.009). Whilst IgG subclasses 1-3 are implicated in infection responses and the bulk of pathogenic autoantibodies, IgG4 is purported to be immunoregulatory. Cis-males demonstrated a higher IgG4:IgG1 serum antibody ratio than cis-females(p=0.003). Oestrogen blockade on an XX background in trans-males resulted in a reduced proportion of class-switched B-cells compared to cis-females(p=0.005), in-line with the cis-male profile. The ratio of IgG1:IgG4 subclasses was unaffected. Interestingly, oestrogen treatment on the XY background of trans-females demonstrated no overall effect on class-switching(p=0.250) but IgG4:IgG1 ratios were decreased significantly(p=0.015). Preliminary mechanistic analysis showed that AICDA(Activation-induced cytidine deaminase, an enzyme essential for CSR DNA mutations) expression was decreased in cis-males(p=0.038), and that oestrogen blockade in trans-males(p=0.125) was associated with a potential reduction, compared to cis-females. No differences were observed following oestrogen treatment in trans-females compared to cis-males(p=0.230). Oestrogen differentially affected B-cell CSR on XX and XY chromosomal backgrounds. Further work is implicated to establish the mechanisms behind this.
| Type: | Poster |
|---|---|
| Title: | Differential impact of sex steroid hormones on B cell class switching, dependant upon sex chromosomal complement |
| Event: | Division of Medicine Research Retreat 2022 |
| Location: | London, UK |
| Dates: | 30 June 2022 |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | https://www.ucl.ac.uk/medicine/news-and-events/res... |
| Language: | English |
| Keywords: | Gender, Sex, B cells, Class switch recombination, autoimmunity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10165978 |
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