The red blood cell as a novel regulator of human B-cell activation.

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

doi:10.1111/imm.13327

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 whilst circulating in the bloodstream.

Highlights

The importance for health of regulating adaptive immune responses is well established, the roles of regulatory lymphocyte populations [1], but the contribution of nonimmune cells to this control is less well defined
Peripheral blood mononuclear cells (PBMC) were separated from red blood cells (RBC), and B-cell expression of HLA-DP/DQ/ DR was measured as a marker of activation at 6 hourly intervals for 24 h and compared with the expression by B cells that had remained in paired samples of whole blood
Freshly isolated B cells already stain strongly for HLA-DR/ DP/DQ (Figure S1a), removal of RBC was associated with a notable increase in expression, which was significant by 12 h, and which typically continued to rise throughout the experiment (Figure 1a)

Summary

Introduction

The importance for health of regulating adaptive immune responses is well established, the roles of regulatory lymphocyte populations [1], but the contribution of nonimmune cells to this control is less well defined. RBC are by far the most abundant cell type in the bloodstream [3], where they are in continuous contact with circulating leucocytes and have the opportunity to deliver regulatory signals. In contrast to the extensive literature describing the immune effects of platelets [4], there are very few reports of the interactions of RBC with innate or adaptive immunity. B cells make up approximately 15% of circulating lymphocytes, and in addition to providing antibody responses, they Evidence has emerged that RBC can inhibit immune cells such as neutrophils [5] and T cells [6], but little is known of their effects on human B cells.

Methods

Results

Conclusion