The IGHV1-69/IGHJ3 recombinations of unmutated CLL are distinct from those of normal B cells

被引：10

作者：

Forconi, Francesco ^{[1
,2
,3
]}

Potter, Kathleen N. ^{[4
]}

Sozzi, Elisa ^{[2
,3
]}

Henderson, Isla ^{[4
]}

Cencini, Emanuele ^{[2
,3
]}

Rossi, Davide ^{[5
]}

Bomben, Riccardo ^{[6
]}

Gattei, Valter ^{[6
]}

Gaidano, Gianluca ^{[5
]}

Packham, Graham

Stevenson, Freda K. ^{[4
]}

机构：

[1] Univ Southampton, Fac Med, Canc Res UK Ctr, Canc Sci Unit,Southhampton Univ Hosp Trust, Southampton S016 6YD, Hants, England

[2] Univ Siena, Dept Clin Med & Immunol Sci, I-53100 Siena, Italy

[3] Azienda Osped Univ Senese, Dept Oncol, Siena, Italy

[4] Univ Southampton, Fac Med, Genet Vaccine Grp, Canc Sci Unit, Southampton SO16 6YD, Hants, England

[5] Amedeo Avogadro Univ Eastern Piedmont, Dept Clin & Expt Med, Div Hematol, Novara, Italy

[6] Ist Ricovero & Cura Carattere Sci, Ctr Riferimento Oncol, Clin & Expt Oncohematol Unit, Aviano, Italy

来源：

BLOOD | 2012年 / 119卷 / 09期

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; HEAVY-CHAIN IIA; SOMATIC HYPERMUTATION; ANTIGEN SELECTION; APOPTOTIC CELLS; GENES; REPERTOIRE; ANTIBODIES; FEATURES; LEUKEMOGENESIS;

D O I：

10.1182/blood-2011-08-375501

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IGHV1-69/51p1 is expressed by similar to 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. (Blood. 2012; 119(9): 2106-2109)

引用

页码：2106 / 2109

页数：4

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