Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse red pulp B cell lymphoma.

Aurélie Verney,Evelyne Callet-Bauchu,Jean-Pierre Magaud,Gilles Salles,Lucile Baseggio,Laurent Genestier,Laurent Jallades,Alexandra Traverse-Glehen

doi:10.18632/oncotarget.25283

Abstract

In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse red pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities.Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeared functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells.In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.

Highlights

Toll-like receptors (TLR) recognize a set of different pathogen-associated molecular patterns derived from viruses, bacteria and fungi [1], as well as from various endogenous molecules and auto-antigens [2]
The present study focused on the Toll-like Receptor (TLR) profile and function in two close splenic lymphomas entities: splenic marginal zone lymphoma (SMZL) and SDRPL
At the mRNA level and in splenic samples, we confirmed the higher expression of TLR9 in SMZL B cells compared to non-tumoral B cells, as previously reported [12], and described for the first time a TLR profile in SDRPL B cells

Summary

Introduction

Toll-like receptors (TLR) recognize a set of different pathogen-associated molecular patterns derived from viruses, bacteria and fungi [1], as well as from various endogenous molecules and auto-antigens [2]. TLR bridge innate and adaptive immune responses by acting as costimulatory signals for B cells and by inducing maturation, proliferation and antibody production [3, 4]. Abnormal TLR expression and/or signaling may play an important role in the pathogenesis of lymphomas, especially in splenic marginal zone lymphoma (SMZL), since TLR pathways are recurrently targeted by genetic changes in this entity [7]. Molecular lesions of signaling pathways have been discovered in chronic B cell lymphoproliferative disorders by generation sequencing (NGS) technology. In addition to TLR, these included B cell receptor (BCR), NOTCH, nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways [8]

Methods

Results

Conclusion