title: The top ten clues to understand the origin of chronic lymphocytic leukemia (CLL).
abstract: The fundamental task of the immune system is to protect the individual from infectious organisms without serious injury to self. The essence of acquired immunity is molecular self/non self discrimination. Chronic lymphocytic leukemia is characterized by a global failure of immune system that begins with the failure of immunological tolerance mechanisms (autoimmunity) and finish with the incapacity to response to non-self antigens (immunodeficiency). Immunological tolerance mechanisms are involved in chronic lymphocytic leukemia (CLL) development. During B cell development some self-reactive B cells acquire a special BCR that recognize their own BCR. This self-autoantibody-self BCR interaction promotes survival, differentiation and proliferation of self-reactive B cells. Continuous self-autoantibody-self BCR interaction cross-linking induces an increased rate of surface BCR elimination, CD5+ expression, receptor editing and anergy. Unfortunately, some times this mechanisms increase genomic instability and promote additional genetic damage that immortalize self-reactive B cells and convert them into CLL like clones with the capability of clonal evolution and transformed CLL B cells. This review summarizes the immunological effects of continuous self-autoantibody-self BCR interaction cross-linking in the surface of self-reactive B cells and their role in CLL development.
authors.affiliation: Hematology Department, Hospital San Pedro, Logroño, La Rioja, Spain. Electronic address: rgmunoz@riojasalud.es.
authors.forename: Ricardo
authors.initials: R
authors.lastname: García-Muñoz
authors.affiliation: Haematology Department, King's College Hospital, London, United Kingdom.
authors.forename: Jesús
authors.initials: J
authors.lastname: Feliu
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
mesh_terms: D000818:Animals; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000276:immunology
keywords: Anergy; Chronic lymphocytic leukemia; Germinal center exclusion; Immunological tolerance theory; Receptor edition; Stem cells