Confrontando argumentos a favor y en contra de antígenos propios y ajenos en la evolución de la subpoblación estereotipada #4 en LLC

• Chiorazzi, N. ^[1]
  1. [1] Feinstein Institute for Medical Research

     Feinstein Institute for Medical Research

     Town of North Hempstead, Estados Unidos

     
• Localización: Revista Hematología, ISSN 0329-0379, ISSN-e 2250-8309, Vol. 22, Nº. Extra 2, 2018 (Ejemplar dedicado a: 3er IBAM CLL 2018), págs. 22-25
• Idioma: español
• Títulos paralelos:
  • Dueling selections for and against auto and foreign antigens in the evolution of CLL stereotyped subset #4
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• Resumen

  • The unique features of the BCRs expressed by CLL B cells have led to the hypothesis that BCRmediated signaling promotes the transformation of a normal B lymphocyte to a CLL B cell(1-3). This is best illustrated by the ~33% of CLL patients grouped into stereotyped subsets based on HCDR3 similarity and the use of similar IGHV-D-J rearrangements(4-6), leading to the assumption that B cells from each subset encountered distinct sets of shared antigenic epitopes that led the way to leukemia. In light of this, a number of autoantigens and exoantigens have been found to bind to CLL BCRs(7-10) and hence could be involved in the survival and proliferation of CLL B-cell clones. However, this view needs to be reconciled with the finding that CLL BCRs appear to universally undergo homotypic interactions (“self-association”) and consequently lead to BCRmediated signaling in the absence of additional nonIG (self)antigens (“autonomous signaling”)(11,12).

    The relationship of these two types of specificities (non-self-IG and self-IG) will be discussed and their effects on the development of the structural elements of the BCRs from a specific stereotyped subset delineated by focusing on stereotyped subset #4. CLL clones in subset #4 bear IGHV4-34/IGHD5-18/IGHJ6 and IGKV2-30/IGKJ2 rearrangements and are always class-switched to IgG and somatically mutated(13,14); they also often exhibit amino acid replacement mutations at defined positions within the antigen-binding site(15). Hence, this subset provides an opportunity to study the influences of a specific IGHV genes and recurrent, restricted somatic mutations on selection for receptor structure and antigen specificity