A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: Molecular and computational evidence

N. Darzentas, A. Hadzidimitriou, F. Murray, K. Hatzi, P. Josefsson, N. Laoutaris, C. Moreno, A. Anagnostopoulos, J. Jurlander, A. Tsaftaris, N. Chiorazzi, C. Belessi, P. Ghia, R. Rosenquist, F. Davi, K. Stamatopoulos

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic lymphocytic leukemia (CLL) is uniquely characterized by the existence of subsets of cases with quasi-identical, stereotyped B-cell receptors (BCRs). Herein we investigate this stereotypy in 2662 patients with CLL, the largest series yet, using purpose-built bioinformatics methods based on sequence pattern discovery. Besides improving the identification of stereotyped cases, we demonstrate that CLL actually consists of two different categories, based on the BCR repertoire, with important biological and ontogenetic differences. The first (30% of cases) shows a very restricted repertoire and is characterized by BCR stereotypy (clustered cases), whereas the second includes cases with heterogeneous BCRs (nonclustered cases). Eleven major CLL clusters were identified with antigen-binding sites defined by just a few critically positioned residues, regardless of the actual immunoglobulin (IG) variable gene used. This situation is closely reminiscent of the receptors expressed by cells participating in innate immune responses. On these grounds, we argue that whereas CLL cases with heterogeneous BCRs likely derive from the conventional B-cell pool, cases with stereotyped BCRs could derive from progenitor cells evolutionarily adapted to particular antigenic challenges, perhaps intermediate between a true innate immune system and the conventional adaptive B-cell immune system, functionally similar to what has been suggested previously for mouse B1 cells.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalLeukemia
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • B-cell receptor
  • CLL
  • Pattern
  • Repertoire
  • Stereotypy

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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