Immunoglobulin Gene Analysis

Chronic lymphocytic leukemia (CLL) represents the most frequent leukemia in the Western world. During the last decade, there has been tremendous progress in elucidating the pathogenesis of this disease. One of the most interesting features discovered during this search is the fact that the leukemia cells express immunoglobulin (IG) that may or may not have incurred somatic hypermutations of the IG heavy variable (IGHV) genes. The outcome of CLL patients with leukemia cells using an unmutated IGHV gene is inferior to those patients with leukemia cells that carry a mutated one. In addition to the important observations relating the IG mutation status to clinical behavior, the fact that the IG repertoire in CLL is restricted and also uniquely characterized by the existence of closely similar, stereotyped B cell receptors implies a role for antigen(s) in leukemogenesis. Recently, it has been found that CLL IG specifically bind certain antigens, including cytoskeletal proteins (vimentin, filamin B, and cofilin 1), but also phosphorylcholine-containing antigens (e.g. Streptococcus pneumonia polysaccharides and oxidized low density lipoprotein). Remarkably, some of these antigens represent molecular motifs exposed on apoptotic cells/blebs and bacteria. Taken together, these data suggest that CD5? CLL B cells may derive from a cell compartment that produces ‘natural antibodies’, which may be instrumental in the elimination and scavenging of apoptotic cells and pathogenic bacteria. Recently, the presence of stereotyped B cell receptors has been linked to clinical features for certain subsets of patients, which implies that particular antigen binding sites may be critical for determining clinical outcome in CLL. Given this dynamic and exciting field of research, this book of Drs Ghia, Rosenquist and Davì is a very timely and important contribution that summarizes the current state of this important research area and its clinical implications, especially in the context of clinical trials. The book results from a very fruitful cooperation of an international group of researchers that has worked together during recent years within the European Research Initiative on CLL (ERIC), also with the aim of standardizing the methodology for a reliable and reproducible assessment of the mutational status of IGHV genes in CLL. I wish this book the wide distribution that it highly deserves. Michael Hallek Direktor, Klinik I für Innere Medizin Universität zu Köln, Germany