The Red Blood Cell as a Novel Regulator of Human B-cell Activation

Charlotte S Lennon; Huan Cao; Andrew M Hall; Mark A Vickers; Robert N Barker

doi:10.1111/imm.13327

The Red Blood Cell as a Novel Regulator of Human B-cell Activation

Charlotte S Lennon, Huan Cao, Andrew M Hall, Mark A Vickers, Robert N Barker^* (Corresponding Author)

^*Corresponding author for this work

University of Aberdeen

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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Abstract

Non‐immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B‐cells. Separation of RBC from peripheral blood mononuclear cells increased B‐cell expression of HLA‐DR/DP/DQ, whilst reconstitution reduced the levels of B‐cell activation markers HLA‐DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B‐cells required contact with RBC and was abrogated by either removal of sialic acids from RBC, or blocking the corresponding lectin receptor CD22 on B‐cells. Chronic lymphocytic leukaemia B‐cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B‐cells while circulating in the bloodstream.

Original language	English
Number of pages	13
Journal	Immunology
Volume	163
Issue number	4
Early online date	6 May 2021
DOIs	https://doi.org/10.1111/imm.13327
Publication status	Published - 1 Aug 2021

Bibliographical note

Acknowledgements
We thank Dr Helen Connaris and Professor Garry Taylor from the University of St Andrews for providing recombinant neuraminidase and Professor Claudia Mauri and Dr Madhvi Menon from Imperial College London for their advice on B‐cell phenotypes. The authors gratefully acknowledge the funding for this project from the Cancer Research Aberdeen North‐East Scotland (CRANES), and from the Wellcome Trust, UK (grant 094847).
Data are available on reasonable request from the corresponding author.

Keywords

immune regulation
B-cell
red blood cell
sialic acid
CD22
human

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abstract = "Non‐immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B‐cells. Separation of RBC from peripheral blood mononuclear cells increased B‐cell expression of HLA‐DR/DP/DQ, whilst reconstitution reduced the levels of B‐cell activation markers HLA‐DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B‐cells required contact with RBC and was abrogated by either removal of sialic acids from RBC, or blocking the corresponding lectin receptor CD22 on B‐cells. Chronic lymphocytic leukaemia B‐cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B‐cells while circulating in the bloodstream.",

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N1 - Acknowledgements We thank Dr Helen Connaris and Professor Garry Taylor from the University of St Andrews for providing recombinant neuraminidase and Professor Claudia Mauri and Dr Madhvi Menon from Imperial College London for their advice on B‐cell phenotypes. The authors gratefully acknowledge the funding for this project from the Cancer Research Aberdeen North‐East Scotland (CRANES), and from the Wellcome Trust, UK (grant 094847). Data are available on reasonable request from the corresponding author.

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N2 - Non‐immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B‐cells. Separation of RBC from peripheral blood mononuclear cells increased B‐cell expression of HLA‐DR/DP/DQ, whilst reconstitution reduced the levels of B‐cell activation markers HLA‐DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B‐cells required contact with RBC and was abrogated by either removal of sialic acids from RBC, or blocking the corresponding lectin receptor CD22 on B‐cells. Chronic lymphocytic leukaemia B‐cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B‐cells while circulating in the bloodstream.

AB - Non‐immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B‐cells. Separation of RBC from peripheral blood mononuclear cells increased B‐cell expression of HLA‐DR/DP/DQ, whilst reconstitution reduced the levels of B‐cell activation markers HLA‐DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B‐cells required contact with RBC and was abrogated by either removal of sialic acids from RBC, or blocking the corresponding lectin receptor CD22 on B‐cells. Chronic lymphocytic leukaemia B‐cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B‐cells while circulating in the bloodstream.

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The Red Blood Cell as a Novel Regulator of Human B-cell Activation

Abstract

Bibliographical note

Keywords

UN SDGs

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