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A different ontogen...
A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors : molecular and computational evidence
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Darzentas, N. (author)
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Hadzidimitriou, A. (author)
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- Murray, Fiona (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Hatzi, K. (author)
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Josefsson, P. (author)
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Laoutaris, N. (author)
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Moreno, C. (author)
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Anagnostopoulos, A. (author)
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Jurlander, J. (author)
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Tsaftaris, A. (author)
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Chiorazzi, N. (author)
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Belessi, C. (author)
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Ghia, Paolo (author)
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- Rosenquist, Richard (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Davi, F. (author)
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Stamatopoulos, K. (author)
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(creator_code:org_t)
- 2009-09-17
- 2010
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 24:1, s. 125-132
- Related links:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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 ( approximately 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- CLL
- B-cell receptor
- stereotypy
- pattern
- repertoire
- Haematology
- Hematologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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Leukemia
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- By the author/editor
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Darzentas, N.
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Hadzidimitriou, ...
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Murray, Fiona
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Hatzi, K.
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Josefsson, P.
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Laoutaris, N.
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show more...
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Moreno, C.
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Anagnostopoulos, ...
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Jurlander, J.
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Tsaftaris, A.
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Chiorazzi, N.
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Belessi, C.
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Ghia, Paolo
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Rosenquist, Rich ...
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Davi, F.
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Stamatopoulos, K ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Leukemia
- By the university
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Uppsala University