Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-01-06

AUTHORS

V Bikos, N Darzentas, A Hadzidimitriou, Z Davis, S Hockley, A Traverse-Glehen, P Algara, A Santoro, D Gonzalez, M Mollejo, A Dagklis, F Gangemi, D S Bosler, G Bourikas, A Anagnostopoulos, A Tsaftaris, E Iannitto, M Ponzoni, P Felman, F Berger, C Belessi, P Ghia, T Papadaki, A Dogan, M Degano, E Matutes, M A Piris, D Oscier, K Stamatopoulos

ABSTRACT

We performed an immunogenetic analysis of 345 IGHV–IGHD–IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele *04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2*04 peaked at 31%. The IGHV1-2*04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2*04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97–99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2*04 allele. More... »

PAGES

1638-1646

Journal

TITLE

Leukemia

ISSUE

7

VOLUME

26

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2012.3

DOI

http://dx.doi.org/10.1038/leu.2012.3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034967212

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22222599


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