Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Selection of antigen receptors in splenic marginal-zone lymphoma: further support from the analysis of the immunoglobulin light-chain gene repertoire

Leukemia volume 26, pages 2567–2569 (2012)Cite this article

Subjects

We recently demonstrated that >30% of the cases with splenic marginal-zone lymphoma (SMZL) express B-cell receptors (BcRs) that carry a single polymorphic variant of the IGHV1-2 gene (IGHV1-2*04).1 The IGHV1-2*04 BcRs in SMZL are characterized by long complementarity-determining region-3 (CDR3) and exhibit a low impact of somatic hypermutation (SHM), leading to limited changes, which cluster in certain positions of the VH domain. Altogether, these features argue for selection by antigen in the pathogenesis of SMZL and suggest heavy chain (HC) dominance in the clonogenic immunoglobulin (IG) receptors of SMZL.1

That notwithstanding, the possibility that IG light chains (IG LC) might also have an important role in SMZL ontogeny exists and needs to be investigated. This is supported by studies demonstrating that IG LCs may be critically implicated in recognition of and selection by antigen. Examples include: (i) significant LC sequence restrictions among estradiol-specific antibodies;2 (ii) impaired responses to Haemophilus influenzae in individuals lacking a specific allelic variant of the IGKV2D-29 gene; and, (iii) biased IG LC gene usage in autoimmunity (for example, IGKV1-17 and IGLV1-47 in lupus,3, 4 IGKV1-39/1D-39 in Graves disease5). Furthermore, the BcR specificity may drastically change through genetic processes affecting LCs, including secondary rearrangements in the context of receptor editing6 or distinctive SHM patterns.7 Finally, marked LC gene repertoire biases exist in various B-cell lymphomas, strongly indicating that LCs can contribute significantly toward shaping antigen reactivity of the clonotypic BcRs.8

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Bikos V, Darzentas N, Hadzidimitriou A, Davis Z, Hockley S, Traverse-Glehen A et al. Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications. Leukemia 2012; 26: 1638–1646.

    Article  CAS  Google Scholar 

  2. Lamminmaki U, Kankare JA . Crystal structure of a recombinant anti-estradiol Fab fragment in complex with 17beta-estradiol. J Biol Chem 2001; 276: 36687–36694.

    Article  CAS  Google Scholar 

  3. Suzuki N, Harada T, Mihara S, Sakane T . Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus. J Clin Invest 1996; 98: 1843–1850.

    Article  CAS  Google Scholar 

  4. Lee J, Cho YJ, Lipsky PE . The V(lambda)-J(lambda) repertoire of patients with systemic lupus erythematosus manifests characteristics of the natural antibody repertoire. Arthritis Rheum 2004; 50: 2604–2614.

    Article  CAS  Google Scholar 

  5. McIntosh RS, Asghar MS, Watson PF, Kemp EH, Weetman AP . Cloning and analysis of IgG kappa and IgG lambda anti-thyroglobulin autoantibodies from a patient with Hashimoto's thyroiditis: evidence for in vivo antigen-driven repertoire selection. J Immunol 1996; 157: 927–935.

    CAS  PubMed  Google Scholar 

  6. Nemazee D . Receptor editing in lymphocyte development and central tolerance. Nat Rev Immunol 2006; 6: 728–740.

    Article  CAS  Google Scholar 

  7. Li H, Jiang Y, Prak EL, Radic M, Weigert M . Editors and editing of anti-DNA receptors. Immunity 2001; 15: 947–957.

    Article  CAS  Google Scholar 

  8. Hadzidimitriou A, Darzentas N, Murray F, Smilevska T, Arvaniti E, Tresoldi C et al. Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia. Blood 2009; 113: 403–411.

    Article  CAS  Google Scholar 

  9. Stamatopoulos K, Belessi C, Papadaki T, Kalagiakou E, Stavroyianni N, Douka V et al. Immunoglobulin heavy- and light-chain repertoire in splenic marginal zone lymphoma. Mol Med 2004; 10: 89–95.

    Article  CAS  Google Scholar 

  10. Traverse-Glehen A, Davi F, Ben Simon E, Callet-Bauchu E, Felman P, Baseggio L et al. Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection. Haematologica 2005; 90: 470–478.

    CAS  Google Scholar 

  11. Swerdlow S, Campo E, Harris NL et al. (eds). WHO Classification of Tumors of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon, France, 2008.

    Google Scholar 

  12. Zibellini S, Capello D, Forconi F, Marcatili P, Rossi D, Rattotti S et al. Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma. Haematologica 2010; 95: 1792–1796.

    Article  CAS  Google Scholar 

  13. Warsame AA, Aasheim HC, Nustad K, Troen G, Tierens A, Wang V et al. Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity. Blood 2011; 118: 3331–3339.

    Article  CAS  Google Scholar 

  14. Baumgarth N, Tung JW, Herzenberg LA . Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin Immunopathol 2005; 26: 347–362.

    Article  CAS  Google Scholar 

  15. Weill JC, Weller S, Reynaud CA . Human marginal zone B cells. Annu Rev Immunol 2009; 27: 267–285.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the ENosAI project (code 09SYN-13-880) co-funded by the EU and the Hellenic General Secretariat for Research and Technology to ND and KS; and the Cariplo Foundation (Milan, Italy) to PG and KS.

Author information

Author notes

  1. V Bikos, E Stalika and P Baliakas: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece

    V Bikos, E Stalika, N Darzentas, A Tsaftaris & K Stamatopoulos

  2. Department of Hematology and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece

    E Stalika, P Baliakas, A Anagnostopoulos & K Stamatopoulos

  3. Molecular Medicine Program, Central European Institute of Technology, Masaryk University, Brno, Czech Republic

    N Darzentas

  4. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK

    Z Davis & D Oscier

  5. Department of Hematopathology, Hospices Civils de Lyon, Université Lyon 1, Lyon, France

    A Traverse-Glehen & F Berger

  6. Division of Molecular Oncology and Department of Onco-Hematology, Laboratory of B cell Neoplasia and Lymphoma Unit, Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy

    A Dagklis & P Ghia

  7. Department of Hematopathology, Evangelismos Hospital, Athens, Greece

    G Kanellis & T Papadaki

  8. Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy

    M Ponzoni

  9. Laboratory of Hematology, Hospices Civils de Lyon, Université Lyon 1, Lyon, France

    P Felman

  10. Department of Hematology, Nikea General Hospital, Piraeus, Greece

    C Belessi

Authors
  1. V Bikos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Stalika
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Baliakas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Darzentas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Z Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Traverse-Glehen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Dagklis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G Kanellis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Anagnostopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Tsaftaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Ponzoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P Felman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P Ghia
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. T Papadaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D Oscier
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. C Belessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. K Stamatopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Stamatopoulos.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bikos, V., Stalika, E., Baliakas, P. et al. Selection of antigen receptors in splenic marginal-zone lymphoma: further support from the analysis of the immunoglobulin light-chain gene repertoire. Leukemia 26, 2567–2569 (2012). https://doi.org/10.1038/leu.2012.207

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2012.207

This article is cited by

Search

Advanced search

Quick links