[Frontiers in Bioscience E4, 2289-2301, January 1, 2012]

Modulation of normal and malignant plasma cells function by toll-like receptors

Gaetan Jego1,2, David Chiron3, Kevin Berthenet1,2, Catherine Pellat-Deceunynck3

1INSERM, U866, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France, 2University of Burgundy, Dijon, France , 3INSERM, U896, Nantes, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Plasma cells are effectors of humoral responses
3.1. Plasma cell differentiation is a multistep process
3.2. Rescuing immature plasma cells from apoptosis in cellular niches
4. Multiple myeloma : a malignant plasmacytosis
5. TLR expression in normal and multiple myeloma plasma cells
6. Could multiple myeloma plasma cells encounter TLR ligands?
7. Function of TLR in normal plasma cells
8. Function of TLR in multiple myeloma cells
8.1. TLR on multiple myeloma cells as protumoral receptors.
8.2. TLR on multiple myeloma cells as therapeutics targets.
9.Conclusion
10. Acknowledgements
11. References

1. ABSTRACT

Toll-like receptors (TLRs) are well known activators of immune responses, but their involvement in the plasma cell (PC) differentiation process remains mostly unknown. This review is focused on the expression and function of TLRs on normal PCs and their malignant counterpart, Multiple Myeloma cells. We report studies that suggest a role for TLR ligands as adjuvants of the humoral immune response through the survival of newly generated immature PCs. On the contrary, TLRs do not seem to be involved in the long-term maintenance of PCs in the bone marrow. Multiple Myeloma cells express a broad range of TLRs, and show heterogeneous responses to different ligands. These double-edged-sword effects are presented and discussed in the context of tumor progression, and as putative therapeutic targets.