Toll-like receptors: lessons to learn from normal and malignant human B cells.
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.
Chiron
David
D
Inserm U892, Nantes, France.
Bekeredjian-Ding
Isabelle
I
Pellat-Deceunynck
Catherine
C
Bataille
Régis
R
Jego
Gaëtan
G
D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D015448:Leukemia, B-Cell / Q000473:pathology; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000473:pathology; D051193:Toll-Like Receptors / Q000276:immunology*
D008024:Ligands; D051193:Toll-Like Receptors