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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2205-2213.
Prepublished online as a Blood First Edition Paper on June 30, 2008; DOI 10.1182/blood-2008-02-140673.
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REVIEW ARTICLE
Toll-like receptors: lessons to learn from normal and malignant human B cells
David Chiron1,
Isabelle Bekeredjian-Ding2,
Catherine Pellat-Deceunynck1,
Régis Bataille1, and
Gaëtan Jego1
1 Inserm U892, Nantes, France; and
2 Department of Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany
The humoral immune system senses microbes via recognition of specific microbial molecular motifs by Toll-like receptors (TLRs). These encounters promote plasma cell differentiation and antibody production. Recent studies have demonstrated the importance of the TLR system in enhancing antibody-mediated defense against infections and maintaining memory B cells. These results have led the way to the design of vaccines that target B cells by engaging TLRs. In hematologic malignancies, cells often retain B cell–specific receptors and associated functions. Among these, TLRs are currently exploited to target different subclasses of B-cell leukemia, and TLR agonists are currently being evaluated in clinical trials. However, accumulating evidence suggests that endogenous TLR ligands or chronic infections promote tumor growth, thus providing a need for further investigations to decipher the exact function of TLRs in the B-cell lineage and in neoplastic B cells. The aim of this review is to present and discuss the latest advances with regard to the expression and function of TLRs in both healthy and malignant B cells. Special attention will be focused on the growth-promoting effects of TLR ligands on leukemic B cells and their potential clinical impact.
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