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Lymphoma

Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inflammatory environment

Leukemia volume 26, pages 1647–1653 (2012)Cite this article

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Abstract

Ocular adnexal marginal zone B-cell lymphomas (OAMZLs) arise in the connective tissues of the orbit or in the mucosa-associated lymphoid tissue of the conjunctiva. Here, we present the immunological and genetic analyses of 20 primary Chlamydia psittaci (Cp)-negative OAMZLs. Analysis of the immunoglobulin variable heavy chain (IgVH) gene usage demonstrated a significant preference for VH4-34. A combined analysis across all previously published OAMZLs confirmed that this is a general feature of OAMZL, in particular of the Cp-negative group. Our series of OAMZLs did not express the characteristic rheumatoid factor VHDJH rearrangements that were previously found in salivary gland- and gastric-marginal zone B-cell lymphomas (MZBCLs). We did not detect the MZBCL-specific chromosomal translocations, t(11;18) API2-MALT1 (mucosa-associated lymphoid tissue1) and t(14;18) IgH/MALT1. Two cases contained a premature stop codon in the A20 gene (TNFAIP3) and one case harbored the activating MYD88 hotspot mutation L265P. Variable nuclear expression of BCL10, NFκB1 (p50) and NFκB2 (p52) suggests that other additional genetic abnormalities affecting the NFκB pathway exist within this group of lymphomas. OAMZL showed variable expression of the chemokine receptor CXCR3 and integrin α4β7 by the tumor B cells, and low interferon-γ and interlukin-4 mRNA levels in the tissue, indicative of an inflammatory environment with features in between those previously found in cutaneous and other extranodal MZBCL. The strongly biased usage of VH4-34 in Cp-negative OAMZLs suggests involvement of a particular stimulatory (auto-) antigen in their development.

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Acknowledgements

We thank Dr C Visser from the Department of Medical Microbiology at the AMC for the Cp diagnostics, R Hoogeboom from the Department of Pathology at the AMC for stimulating discussions and Drs YC Wu and DK Dunn-Walters from the Department of Immunobiology, King's College London School of Medicine, London, UK for their data set of germline IgVH genes of normal B-cell subpopulations.

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Authors and Affiliations

  1. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    F van Maldegem, T A M Wormhoudt, M M S Mulder, M E C M Oud, E Schilder-Tol, A R Musler, J Aten, S T Pals, C J M van Noesel & R J Bende

  2. Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    P Saeed

  3. Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    M J Kersten

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  1. F van Maldegem
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van Maldegem, F., Wormhoudt, T., Mulder, M. et al. Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inflammatory environment. Leukemia 26, 1647–1653 (2012). https://doi.org/10.1038/leu.2012.28

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