Toll-like receptors: lessons to learn from normal and malignant human B cells

• Published in: Blood Vol. 112; no. 6; pp. 2205 - 2213
• Main Authors: Chiron, David, Bekeredjian-Ding, Isabelle, Pellat-Deceunynck, Catherine, Bataille, Régis, Jego, Gaëtan
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.09.2008; The Americain Society of Hematology; American Society of Hematology
• Series: Review Article
• Subjects: Antibody Formation; B-Lymphocytes - immunology; Biological and medical sciences; Cancer; Hematologic and hematopoietic diseases; Hematology; Human health and pathology; Humans; Leukemia, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Ligands; Lymphoma, B-Cell - pathology; Medical sciences; Review; Toll-Like Receptors - immunology; Human; Cell proliferation; Immune response; Hematology; Leukemia; Toll like receptor; Malignant hemopathy; B-Lymphocyte; Review; Carcinogenesis; Infection; Leukemogenesis; Humoral immunity; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-02-140673

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.