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

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

0006-4971
2106-2109
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Henderson, Isla
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Cencini, Emanuele
3dc5d188-96b0-4f7d-abb8-af4d22638d7e
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Bomben, Riccardo
2de7f588-50b7-43f6-8bb9-ec0a0896b8e5
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Henderson, Isla
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Cencini, Emanuele
3dc5d188-96b0-4f7d-abb8-af4d22638d7e
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Bomben, Riccardo
2de7f588-50b7-43f6-8bb9-ec0a0896b8e5
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

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)

Record type: Article

Abstract

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.

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e-pub ahead of print date: 10 January 2012
Published date: 1 March 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 339303
URI: https://eprints.soton.ac.uk/id/eprint/339303
ISSN: 0006-4971
PURE UUID: 983ccb12-9d2a-4fed-8179-6b3f7bace934
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 25 May 2012 13:40
Last modified: 31 Jul 2019 00:50

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Contributors

Author: Elisa Sozzi
Author: Isla Henderson
Author: Emanuele Cencini
Author: Davide Rossi
Author: Riccardo Bomben
Author: Valter Gattei
Author: Gianluca Gaidano
Author: Graham Packham ORCID iD

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