Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement

Peckham, H.; Radziszewska, A.; de Gruijter, N. M.; Restuadi, R.; Kartawinata, M.; Robinson, G. A.; Martin-Gutierrez, L.; Deakin, C. T.; Wedderburn, L. R.; Jury, E. C.; Butler, G.; Rosser, E. C.; Ciurtin, C.

doi:10.1101/2024.07.18.604160

bioRxiv · 10.1101/2024.07.18.604160

Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement

Peckham, H.·Radziszewska, A.·de Gruijter, N. M.·Restuadi, R.·Kartawinata, M.·Robinson, G. A.·Martin-Gutierrez, L.·Deakin, C. T.·Wedderburn, L. R.·Jury, E. C.·Butler, G.·Rosser, E. C.·Ciurtin, C.

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Abstract

Sex differences in humoral immunity are well-documented, though the mechanisms underpinning these differences remain ill-defined. Here, we demonstrate that post-pubertal cisgender females have higher levels of class-switched B cells compared to age-matched cisgender males. However, whilst sex chromosome-encoded genes characterise most of the differences in total B cell transcriptomes between cisgender-females and -males, sex differences in class-switched B cells are only observed post-pubertally. Accordingly, B cells express high levels of oestrogen receptor 2 (ESR2) and genes known to regulate B cell class-switching are enriched for ESR2-binding sites. Using a gender-diverse cohort of young people, we show that in transgender males (XX chromosomal background), blockade of natal oestrogen reduced the frequency of class-switched B cells, whilst gender-affirming oestradiol treatment in transgender females (XY chromosomal background), did not increase the frequency of class-switched B cells. These data demonstrate that sex hormones and chromosomes work in tandem to impact immune responses, with oestrogen only supporting B cell class-switching on an XX chromosomal background. eTOC summarySex hormones and chromosomes work in tandem to impact immune responses, with oestrogen influencing B cell class-switching exclusively on an XX chromosomal background.

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Peckham, H., Radziszewska, A., de Gruijter, N. M., Restuadi, R., Kartawinata, M., Robinson, G. A., Martin-Gutierrez, L., Deakin, C. T., Wedderburn, L. R., Jury, E. C., Butler, G., Rosser, E. C., Ciurtin, C.. 2024-07-22. Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement. https://doi.org/10.1101/2024.07.18.604160

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