title: BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders.
abstract: B cell-activating factor receptor (BAFF-R) is one of three known receptors for BAFF, a critical regulator of B- and T-cell function. In mice, BAFF-R is required for B-cell maturation and survival, and in mice and humans, the overproduction of BAFF is associated with autoimmune disease. We sought to determine the normal pattern of BAFF-R expression at specific stages of B- and T-cell development and whether this pattern of expression corresponds with related B- and T-cell neoplasms. Most circulating human B cells and a small subset of T cells are BAFF-R-positive. In reactive lymphoid tissues, BAFF-R is expressed by B cells colonizing the mantle zones, by a subset of cells within germinal centers, and rare cells in the interfollicular T-cell zone. BAFF-R is also expressed by B cells colonizing the splenic marginal zone. Seventy-seven (78%) of 116 cases of B-cell lymphoproliferative disorders were BAFF-R-positive by immunohistochemical and/or flow cytometric immunophenotypic analysis, including most cases of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and diffuse large B-cell lymphoma. In contrast, cases of precursor B lymphoblastic lymphoma, Burkitt lymphoma, and nodular lymphocyte-predominant Hodgkin lymphoma exhibit weak to negative staining for BAFF-R. All cases of classical Hodgkin lymphoma and T-cell lymphomas were BAFF-R-negative, including all cases of anaplastic large cell lymphoma, adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, unspecified. These findings highlight BAFF-R as a marker of both normal and neoplastic B cells and raise the possibility that BAFF-R expression is necessary for the survival of a subset of neoplastic B lymphocytes analogous to its known role in promoting normal B-cell maturation and survival.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Ali
authors.initials: A
authors.lastname: Shahsafaei
authors.forename: Betty
authors.initials: B
authors.lastname: Li
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008232:Lymphoproliferative Disorders / Q000145:classification / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019948:Receptors, Interleukin-4