Reduced CD27-IgD- B cells in blood and raised CD27-IgD- B cells in gut-associated lymphoid tissue in inflammatory bowel disease.

Chathyan Pararasa; Na Zhang; Thomas Justin Tull; Ming HA Chong; Jacqueline HY Siu; William Wilfried Jonathan Guesdon; Konstantia-Maria Chavele; Jeremy Sanderson; Louise Langmead; Klaartje Kok; Jo Michele Spencer; anna vossenkamper

doi:10.3389/fimmu.2019.00361

Reduced CD27-IgD- B cells in blood and raised CD27-IgD- B cells in gut-associated lymphoid tissue in inflammatory bowel disease.

Chathyan Pararasa, Na Zhang, Thomas Justin Tull, Ming HA Chong, Jacqueline HY Siu, William Wilfried Jonathan Guesdon, Konstantia-Maria Chavele, Jeremy Sanderson, Louise Langmead, Klaartje Kok, Jo Michele Spencer, anna vossenkamper

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Abstract

The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD.

Here we analysed B cells in blood of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analysed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27-IgD- B cells expressing all Ig isotypes in the blood in IBD (independent of severity of disease and treatment) compared to healthy controls. Successful treatment of patients with biologic therapies did not change the profile of B cell subsets in blood. By mass cytometry we demonstrated that CD27-IgD- B cells were proportionately enriched in the gut-associated lymphoid tissue (GALT) in IBD. Since production of TNF is a feature of IBD relevant to therapies, we sought to determine whether B cells in GALT or the CD27-IgD- subset in particular could contribute to pathology by secretion of TNF or IL-10. We found that donor matched GALT and blood B cells are capable of producing TNF as well as IL-10, but we saw no evidence that CD27-IgD- B cells from blood expressed more TNF compared to other subsets.

The reduced proportion of CD27-IgD- B cells in blood and the increased proportion in the gut implies that CD27-IgD- B cells are recruited from the blood to the gut in IBD. CD27-IgD- B cells have been implicated in immune responses to intestinal bacteria and recruitment to GALT,
and may contribute to the intestinal inflammatory milieu in IBD.

Original language	English
Article number	361
Journal	Frontiers in Immunology
Volume	10
DOIs	https://doi.org/10.3389/fimmu.2019.00361
Publication status	Published - 5 Mar 2019

Keywords

GALT
biologics
inflammatory bowel disease
infliximab
mass cytometry
memory B cells
ustekinumab

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Reduced CD27−IgD− B_PARARASA_Accepted 12 February 2019_GOLD VoR (CC BY)Final published version, 4.62 MBLicence: CC BY

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Pararasa, C., Zhang, N., Tull, T. J., Chong, M. HA., Siu, J. HY., Guesdon, W. W. J., Chavele, K.-M., Sanderson, J., Langmead, L., Kok, K., Spencer, J. M., & vossenkamper, A. (2019). Reduced CD27-IgD- B cells in blood and raised CD27-IgD- B cells in gut-associated lymphoid tissue in inflammatory bowel disease. Frontiers in Immunology, 10, Article 361. https://doi.org/10.3389/fimmu.2019.00361

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abstract = "The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analysed B cells in blood of patients with Crohn{\textquoteright}s disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analysed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27-IgD- B cells expressing all Ig isotypes in the blood in IBD (independent of severity of disease and treatment) compared to healthy controls. Successful treatment of patients with biologic therapies did not change the profile of B cell subsets in blood. By mass cytometry we demonstrated that CD27-IgD- B cells were proportionately enriched in the gut-associated lymphoid tissue (GALT) in IBD. Since production of TNF is a feature of IBD relevant to therapies, we sought to determine whether B cells in GALT or the CD27-IgD- subset in particular could contribute to pathology by secretion of TNF or IL-10. We found that donor matched GALT and blood B cells are capable of producing TNF as well as IL-10, but we saw no evidence that CD27-IgD- B cells from blood expressed more TNF compared to other subsets. The reduced proportion of CD27-IgD- B cells in blood and the increased proportion in the gut implies that CD27-IgD- B cells are recruited from the blood to the gut in IBD. CD27-IgD- B cells have been implicated in immune responses to intestinal bacteria and recruitment to GALT, and may contribute to the intestinal inflammatory milieu in IBD. ",

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AU - Guesdon, William Wilfried Jonathan

AU - Chavele, Konstantia-Maria

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AB - The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analysed B cells in blood of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analysed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27-IgD- B cells expressing all Ig isotypes in the blood in IBD (independent of severity of disease and treatment) compared to healthy controls. Successful treatment of patients with biologic therapies did not change the profile of B cell subsets in blood. By mass cytometry we demonstrated that CD27-IgD- B cells were proportionately enriched in the gut-associated lymphoid tissue (GALT) in IBD. Since production of TNF is a feature of IBD relevant to therapies, we sought to determine whether B cells in GALT or the CD27-IgD- subset in particular could contribute to pathology by secretion of TNF or IL-10. We found that donor matched GALT and blood B cells are capable of producing TNF as well as IL-10, but we saw no evidence that CD27-IgD- B cells from blood expressed more TNF compared to other subsets. The reduced proportion of CD27-IgD- B cells in blood and the increased proportion in the gut implies that CD27-IgD- B cells are recruited from the blood to the gut in IBD. CD27-IgD- B cells have been implicated in immune responses to intestinal bacteria and recruitment to GALT, and may contribute to the intestinal inflammatory milieu in IBD.

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KW - mass cytometry

KW - memory B cells

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Reduced CD27-IgD- B cells in blood and raised CD27-IgD- B cells in gut-associated lymphoid tissue in inflammatory bowel disease.

Abstract

Keywords

UN SDGs

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