Immunoglobulin gene repertoire in ocular adnexal lymphomas: Hints on the nature of the antigenic stimulation

A. Dagklis, M. Ponzoni, S. Govi, M. G. Cangi, E. Pasini, F. Charlotte, A. Vino, C. Doglioni, F. Davì, Izidore Lossos, I. Ntountas, T. Papadaki, R. Dolcetti, A. J M Ferreri, K. Stamatopoulos, P. Ghia

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

Original languageEnglish
Pages (from-to)814-821
Number of pages8
JournalLeukemia
Volume26
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

Marginal Zone B-Cell Lymphoma
Immunoglobulin Genes
Chlamydophila psittaci
Lymphoma
Chlamydophila Infections
B-Lymphocytes
Immunoglobulins
Chlamydophila
B-Cell Lymphoma
B-Cell Chronic Lymphocytic Leukemia
Autoantibodies
Clone Cells
Binding Sites
Ligands
Antigens
DNA
Infection

Keywords

  • Chlamydia psittaci
  • immunoglobulins
  • ocular adnexa lymphoma

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Dagklis, A., Ponzoni, M., Govi, S., Cangi, M. G., Pasini, E., Charlotte, F., ... Ghia, P. (2012). Immunoglobulin gene repertoire in ocular adnexal lymphomas: Hints on the nature of the antigenic stimulation. Leukemia, 26(4), 814-821. https://doi.org/10.1038/leu.2011.276

Immunoglobulin gene repertoire in ocular adnexal lymphomas : Hints on the nature of the antigenic stimulation. / Dagklis, A.; Ponzoni, M.; Govi, S.; Cangi, M. G.; Pasini, E.; Charlotte, F.; Vino, A.; Doglioni, C.; Davì, F.; Lossos, Izidore; Ntountas, I.; Papadaki, T.; Dolcetti, R.; Ferreri, A. J M; Stamatopoulos, K.; Ghia, P.

In: Leukemia, Vol. 26, No. 4, 01.04.2012, p. 814-821.

Research output: Contribution to journalArticle

Dagklis, A, Ponzoni, M, Govi, S, Cangi, MG, Pasini, E, Charlotte, F, Vino, A, Doglioni, C, Davì, F, Lossos, I, Ntountas, I, Papadaki, T, Dolcetti, R, Ferreri, AJM, Stamatopoulos, K & Ghia, P 2012, 'Immunoglobulin gene repertoire in ocular adnexal lymphomas: Hints on the nature of the antigenic stimulation', Leukemia, vol. 26, no. 4, pp. 814-821. https://doi.org/10.1038/leu.2011.276
Dagklis, A. ; Ponzoni, M. ; Govi, S. ; Cangi, M. G. ; Pasini, E. ; Charlotte, F. ; Vino, A. ; Doglioni, C. ; Davì, F. ; Lossos, Izidore ; Ntountas, I. ; Papadaki, T. ; Dolcetti, R. ; Ferreri, A. J M ; Stamatopoulos, K. ; Ghia, P. / Immunoglobulin gene repertoire in ocular adnexal lymphomas : Hints on the nature of the antigenic stimulation. In: Leukemia. 2012 ; Vol. 26, No. 4. pp. 814-821.
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abstract = "Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40{\%} Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11{\%}) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.",
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AU - Cangi, M. G.

AU - Pasini, E.

AU - Charlotte, F.

AU - Vino, A.

AU - Doglioni, C.

AU - Davì, F.

AU - Lossos, Izidore

AU - Ntountas, I.

AU - Papadaki, T.

AU - Dolcetti, R.

AU - Ferreri, A. J M

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AU - Ghia, P.

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