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

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.

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha

“…While other studies have demonstrated the functional role of IL-1 and signaling pathway of TLR4 in astrocytes 51,52 , to our knowledge, this is the first time the critical autocrine/paracrine effects of TNF-α on astrocyte functioning are demonstrated. In addition, other studies have demonstrated the roles of TLRs, including TLR2 and TLR4, in upregulating proliferation in various cancers [53][54][55][56] , to our knowledge, we are the first to demonstrate their significance in the transition between quiescent and proliferative astrocytes via the production of TNF-α. Our findings will likely delineate the cellular and molecular mechanisms involved in different neurological conditions.…”

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas

“…This study demonstrates the necessity of a more profound understanding of immune effectors in SMZL TME. Other studies have concerned the innate immune system; one of them from Verney et al identified distinct TLRs profiles in SMZLs [ 80 ]. The dense CD40 expression by bone marrow stromal cells (involving CD40 ligand expressed by mast cells) is correlated with a poorer prognosis [ 81 ].…”