From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity ☆ Paolo Ghia ⁎ , Cristina Scielzo, Michela Frenquelli, Marta Muzio, Federico Caligaris-Cappio Unit of Lymphoid Malignancies, Department of Oncology, Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy Available online 22 March 2007 Abstract Chronic lymphocytic leukemia (CLL) is a B-cell malignancy endowed with a number of features that recall autoimmune disorders, including the CD5 expression and the development of autoimmune manifestations restricted to self antigens expressed by hematopoietic cells. Several evidences strongly support the possibility that an antigenic stimulation through the B- cell receptor (BCR) is involved in the selection and possibly also the expansion of the malignant clone. Though all evidences suggest specific Ag recognition and possibly stimulation at different time-points, the nature of the Ag(s) is still unknown. It appears likely that CLL cells derive from a pool of auto/polyreactive CD5 + B cells. Hence CLL appears to be a B-cell malignancy triggered or facilitated in its development and evolution by an auto-Ag. The crucial issues have become to what extent this deleterious binding capacity is central to the natural history of the disease and how it relates to the malignant transformation of the cell. © 2007 Elsevier B.V. All rights reserved. Keywords: Chronic lymphocytic leucemia; B lymphocytes; CD5; Immunoglobulin receptor; Auto-antigen Contents 1. Introduction ...................................................... 128 2. The issue of CD5 ................................................... 128 3. CD5 as an activation marker? ............................................. 128 4. Autoimmune manifestations in CLL .......................................... 128 5. Immunoglobulin receptors in CLL ........................................... 129 6. The issue of the antigen ................................................ 129 7. Conclusions and perspectives ............................................. 129 Take-home messages .................................................... 130 References ............................................................ Available online at www.sciencedirect.com Autoimmunity Reviews 7 (2007) 127 – 131 www.elsevier.com/locate/autrev ☆ This work was supported by Associazione Italiana per la Ricerca sul Cancro, Fondazione Anna Villa e Felice Rusconi, CLL Global Research Foundation, MIUR. ⁎ Corresponding author. Università Vita-Salute San Raffaele, c/o DIBIT 4A 3, Via Olgettina 58, 20132, Milano, Italy. Tel.: +39 02 2643 4797; fax: +39 02 2643 4723. E-mail address: ghia.paolo@hsr.it (P. Ghia). 130 1568-9972/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2007.02.014