CD200R1 and CD200R1L expression is regulated during B cell development in swine and modulates the Ig production in response to the TLR7 ligand imiquimoid.

Teresa Poderoso,Belén Álvarez,Concepción Revilla,Paloma Martínez De La Riva,Javier Domínguez,Ángel Ezquerra

doi:10.1371/journal.pone.0251187

Teresa Poderoso, Belén Álvarez + Show 4 more

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https://doi.org/10.1371/journal.pone.0251187

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Abstract

The CD200R family comprises a group of paired receptors that can modulate the activation of immune cells. They are expressed both on myeloid cells and lymphocyte subsets. Here we report that the expression of these receptors on porcine B cells is tightly regulated, being mainly expressed on mature cells. The expression of the inhibitory receptors CD200R1 and/or its splicing variant CD200R1X2, either in combination or not with the activating receptor CD200R1L, is upregulated in sIgM+ effector/memory cells, and tends to decline thereafter as these cells progress to plasmablasts or switch the Ig isotype. sIgM+ naïve and primed cells only express, by contrast, the CD200R1X2 receptor. B-1 like cells also express CD200R1 isoforms, either alone or in combination with CD200R1L. Treatment of peripheral blood mononuclear cells with a monoclonal antibody specific for inhibitory receptors, enhances the IgM and IgG production induced by TLR7 stimulation suggesting a modulatory role of B cell functions of these receptors.

Highlights

Cells of the immune system express a variety of paired receptors characterised by sharing a high sequence identity in their extracellular regions while differing in their transmembrane and cytosolic domains, which trigger opposing inhibitory and activating pathways [1]
Previous studies in our laboratory have shown that porcine CD200R1 isoforms and/or CD200R1L are expressed on a significant proportion of peripheral blood B cells [19]
When we analysed the reactivity of PCT1 and PCT3 monoclonal antibodies (mAbs) on these subpopulations (Fig 1A and 1B), naïve (CD2+CD21b+) and primed (CD2-CD21b+) B cells were mostly PCT1 negative, and they do express neither CD200R1 nor CD200R1L at the cell surface

Summary

Introduction

Cells of the immune system express a variety of paired receptors characterised by sharing a high sequence identity in their extracellular regions while differing in their transmembrane and cytosolic domains, which trigger opposing inhibitory and activating pathways [1]. Signals from these receptors can synergize with, antagonize or modulate those from other receptors, and their opposing functions provide the immune system with a mechanism to “fine-tune” innate and adaptive immunity, ensuring an effective response against pathogens while restraining detrimental effects to the host. CD200R1 contains three tyrosine residues in its cytoplasmic tail, through which it can recruit the adaptor molecule Dok and activate RasGAP, leading to inhibition of the ERK

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