The IGHV1-69/IGHJ3 recombinations of unmutated CLL are distinct from those of normal B cells
Forconi, Francesco, Potter, Kathleen N., Sozzi, Elisa, Henderson, Isla, Cencini, Emanuele, Rossi, Davide, Bomben, Riccardo, Gattei, Valter, Gaidano, Gianluca, Packham, Graham and Stevenson, Freda K. (2012) The IGHV1-69/IGHJ3 recombinations of unmutated CLL are distinct from those of normal B cells. Blood, 119, (9), 2106-2109. (doi:10.1182/blood-2011-08-375501). (PMID:22234701).
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IGHV1-69/51p1 is expressed by ∼ 30% of unmutated chronic lymphocytic leukemia (U-CLL) and combines with selected IGHD and IGHJ genes generating stereotypes if HCDR3 amino acid homology is > 60%. We had previously revealed stereotypic IGHV1-69/IGHJ6 rearrangements in normal naive B cells, thereby identifying potential counterparts of U-CLL. A different stereotypic IGHV1-69/IGHD3-16(RF2)/IGHJ3 rearrangement carrying the CAR(GGx)YD motif in the N1-region, recurrent in 6% IGHV1-69+ve CLL, is exceptionally sequence restricted, strongly suggestive of shared antigen recognition. We have now analyzed IGHV1-69/IGHJ3 rearrangements in circulating B cells of healthy individuals using several PCR-based approaches with IGHV1-69/IGHJ3 CLL sequences for reference. Stereotypes were found, but all were distinct from CLL. Remarkably, even a highly sensitive semi-nested PCR, specific for the CLL-expressed IGHV1-69/IGHD3-16(RF2)/IGHJ3 stereotype, failed to identify the CAR(GGx)YD sequence, although similar motifs were found. These highly specific B cells are not apparent in the accessible normal repertoire and may expand in response to rarely expressed antigens important in the pathogenesis of CLL.
|Subjects:||R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||Faculty of Medicine > Cancer Sciences
|Date Deposited:||25 May 2012 13:40|
|Last Modified:||26 Jul 2012 00:51|
|Contributors:||Forconi, Francesco (Author)
Potter, Kathleen N. (Author)
Sozzi, Elisa (Author)
Henderson, Isla (Author)
Cencini, Emanuele (Author)
Rossi, Davide (Author)
Bomben, Riccardo (Author)
Gattei, Valter (Author)
Gaidano, Gianluca (Author)
Packham, Graham (Author)
Stevenson, Freda K. (Author)
|Date:||1 March 2012|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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