Human Pathology
Volume 41, Issue 2 , Pages 271-280, February 2010

CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas

  • Robert F. Luo, MD, MPH

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Shuchun Zhao, MS

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Robert Tibshirani, PhD

      Affiliations

    • Department of Health Research and Policy and Statistics, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • June H. Myklebust, PhD

      Affiliations

    • Division of Oncology, Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Mrinmoy Sanyal, PhD

      Affiliations

    • Division of Oncology, Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Rosemary Fernandez

      Affiliations

    • Division of Oncology, Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Dita Gratzinger, MD, PhD

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Robert J. Marinelli, PhD

      Affiliations

    • Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Zhi Shun Lu, MS

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Anna Wong, MD

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Ronald Levy, MD

      Affiliations

    • Division of Oncology, Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • ,
  • Shoshana Levy, PhD

      Affiliations

    • Division of Oncology, Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
    • These authors contributed equally.
  • ,
  • Yasodha Natkunam, MD, PhD

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    • Corresponding Author InformationCorresponding author.
    • These authors contributed equally.

Received 8 May 2009; received in revised form 28 July 2009; accepted 30 July 2009. published online 09 December 2009.

Summary 

CD81 is a tetraspanin cell surface protein that regulates CD19 expression in B lymphocytes and enables hepatitis C virus infection of human cells. Immunohistologic analysis in normal hematopoietic tissue showed strong staining for CD81 in normal germinal center B cells, a cell type in which its increased expression has not been previously recognized. High-dimensional flow cytometry analysis of normal hematopoietic tissue confirmed that among B- and T-cell subsets, germinal center B cells showed the highest level of CD81 expression. In more than 800 neoplastic tissue samples, its expression was also found in most non-Hodgkin lymphomas. Staining for CD81 was rarely seen in multiple myeloma, Hodgkin lymphoma, or myeloid leukemia. In hierarchical cluster analysis of diffuse large B-cell lymphoma, staining for CD81 was most similar to other germinal center B cell–associated markers, particularly LMO2. By flow cytometry, CD81 was expressed in diffuse large B-cell lymphoma cells independent of the presence or absence of CD10, another germinal center B-cell marker. The detection of CD81 in routine biopsy samples and its differential expression in lymphoma subtypes, particularly diffuse large B-cell lymphoma, warrant further study to assess CD81 expression and its role in the risk stratification of patients with diffuse large B-cell lymphoma.

Keywords: CD81, Lymphoma, Tissue microarray

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 Support: This work was partly funded by NIH CA34233, CA33399, and the Leukemia and Lymphoma Society SCORE grant. RL is an American Cancer Society Clinical Research Professor and JHM is a Norwegian Cancer Society Fellow.

PII: S0046-8177(09)00285-8

doi:10.1016/j.humpath.2009.07.022

Human Pathology
Volume 41, Issue 2 , Pages 271-280, February 2010