title: Expression of SHP-1 phosphatase indicates post-germinal center cell derivation of B-cell posttransplant lymphoproliferative disorders.
abstract: SHP-1 tyrosine phosphatase acts as a negative regulator of signaling by receptors for growth factors, cytokines, and chemokines and by receptors involved in immune response. Our recent study showed that SHP-1 is tightly regulated at various stages of B-cell differentiation and is expressed in the mantle and marginal zones, interfollicular B cells, and plasma cells, whereas it is nondetectable in germinal center cells. In this study we evaluated expression of SHP-1 in vitro and in vivo in nine cell lines representing three different types of EBV+ B-cell populations closely resembling or derived from posttransplant lymphoproliferative disorders (PTLDs). Furthermore, we examined tissue samples from 58 patients with B-cell PTLDs, both EBV+ (85% of the cases analyzed) and EBV- (15%). SHP-1 protein was strongly expressed in all cell lines and PTLD cases. In addition, the PTLD cases were essentially negative for germinal center B-cell markers: none expressed CD10 and only one expressed BCL-6. More than 40% expressed a late post-germinal B-cell marker, CD138. The universal expression of SHP-1, lack of expression of CD10 and BCL-6, and frequent expression of CD138 suggest that PTLDs are derived from post-germinal center B cells regardless of the EBV cell infection status. Based on the immunophenotype, B-cell PTLDs could be divided into two broad categories corresponding to the early (CD10-/BCL-6-/SHP-1+/CD138-) and late (CD10-/BCL-6-/SHP-1+/CD138+) post-germinal center cells. By being expressed earlier, SHP-1 is a more sensitive marker of post-germinal center B cells than CD138, which is seen on the terminally differentiated immunoblasts and plasma cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Paessler
authors.forename: Plamen
authors.initials: P
authors.lastname: Kossev
authors.forename: Donald
authors.initials: D
authors.lastname: Tsai
authors.forename: Puthiaveetil
authors.initials: P
authors.lastname: Raghunath
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Majewski
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Preetha
authors.initials: P
authors.lastname: Ramalingam
authors.forename: Stephen
authors.initials: S
authors.lastname: Schuster
authors.forename: John
authors.initials: J
authors.lastname: Tomaszewski
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.forename: Eric
authors.initials: E
authors.lastname: Hsi
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis; D018858:Germinal Center / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000032:analysis; D015260:Neprilysin / Q000032:analysis; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000175:diagnosis* / Q000201:enzymology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000032:analysis* / Q000502:physiology; D011509:Proteoglycans / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D015260:Neprilysin