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Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa

Papoutsopoulou, Stamatia; Tang, Joseph; Elramli, Ahmed H.; Williams, Jonathan M.; Gupta, Nitika; Ikuomola, Felix I.; Sheibani-Tezerji, Raheleh; Alam, Mohammad T.; Hernández-Fernaud, Juan R.; Caamaño, Jorge H.; Probert, Chris S.; Muller, Werner; Duckworth, Carrie A.; Pritchard, D. Mark


Stamatia Papoutsopoulou

Joseph Tang

Ahmed H. Elramli

Jonathan M. Williams

Nitika Gupta

Felix I. Ikuomola

Raheleh Sheibani-Tezerji

Mohammad T. Alam

Juan R. Hernández-Fernaud

Jorge H. Caamaño

Chris S. Probert

Werner Muller

Carrie A. Duckworth

D. Mark Pritchard


Jonathan Williams


Background & aims: The alternative (non-canonical) nuclear factor-kB (NF-kB) signalling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline Nfkb2 deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, including azoxymethane/dextran sulfate sodium (DSS)-induced colitis-associated cancer and lipopolysaccharide (LPS)-induced small intestinal epithelial apoptosis. However, the common underlying protective mechanisms have not yet been fully elucidated. Methods: We applied high throughput RNASeq and proteomic analyses to characterise the transcriptional and protein signatures of the small intestinal mucosa of naïve adult Nfkb2-/- mice. Those data were validated by immunohistochemistry and quantitative ELISA using both small intestinal tissue lysates and serum. Results: We identified a B-lymphocyte defect as a major transcriptional signature in the small intestinal mucosa and immunoglobulin A as the most downregulated protein by proteomic analysis in Nfkb2-/- mice. Small intestinal immunoglobulins were dramatically dysregulated, with undetectable levels of immunoglobulin A and greatly increased amounts of immunoglobulin M being detected. The numbers of IgA-producing, CD138+ve plasma cells were also reduced in the lamina propria of the small intestinal villi of Nfkb2-/- mice. This phenotype was even more striking in the small intestinal mucosa of RelB-/- mice, although these mice were equally sensitive to LPS-induced intestinal apoptosis as their RelB+/+ wild-type counterparts. Conclusions: NF-kB2/p52 deficiency confers resistance to LPS-induced small intestinal apoptosis and also appears to regulate the plasma cell population and immunoglobulin levels within the gut.


Papoutsopoulou, S., Tang, J., Elramli, A. H., Williams, J. M., Gupta, N., Ikuomola, F. I., …Pritchard, D. M. (2022). Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa. American Journal of Physiology - Gastrointestinal and Liver Physiology, 323(4), G306-G317.

Journal Article Type Article
Acceptance Date Jul 22, 2022
Publication Date Oct 1, 2022
Deposit Date Sep 13, 2022
Publicly Available Date Sep 27, 2022
Journal American Journal of Physiology-Gastrointestinal and Liver Physiology
Print ISSN 0193-1857
Electronic ISSN 1522-1547
Publisher American Physiological Society
Peer Reviewed Peer Reviewed
Volume 323
Issue 4
Pages G306-G317
Keywords Physiology (medical); Gastroenterology; Hepatology; Physiology
Additional Information Received: 2022-02-10; Revised: 2022-07-19; Accepted: 2022-07-19; Published: 2022-09-12


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