Infrequent “chronic lymphocytic leukemia-specific” immunoglobulin stereotypes in aged individuals with or without low count monoclonal B cell lymphocytosis

Chronic lymphocytic leukemia (CLL) is characterized by the existence of stereotyped B cell receptor immunoglobulins (BcR IG), strongly supporting a role for antigens in disease ontogeny. That said, it remains inconclusive whether stereotyped receptors occur in the repertoire of unaffected elderly individuals, particularly in “CLL­like” low-count monoclonal B cell lymphocytosis (LC-MBL) that may represent an early stage in the natural history of CLL. Previous immunogenetic studies reported the presence of some CLL stereotypes in the repertoire of healthy individuals, as well as a low incidence of stereotypy in LC­MBL. However, these studies were Sanger-based, thus, leaving the issue open regarding the presence of “CLL-related” stereotypes in healthy individuals.In this context, we performed a systematic analysis of the BcR IG repertoire using next generation sequencing (NGS) methodologies of: (i) clonal and normal B cell populations in individuals with “CLL­like” LC­MBL and (ii) naïve, memory and total B cells from age-matched, healthy individuals without LC­MBL.