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:||04 Oct 2013 10:40|
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