PRDM1/Blimp‐1 is expressed in human B‐lymphocytes committed to the plasma cell lineage

PRDM1/Blimp‐1 (in human and mouse, respectively) has a central role in determining and shaping the secretory arm of mature B‐cell differentiation. In this study, a mouse monoclonal antibody that recognizes PRDM1 was used to detail its distribution in normal human lymphoid tissue and in lymphoid neoplasms that correspond to different stages of B‐cell differentiation. PRDM1 was expressed in germinal centre blasts that co‐express Pax5, CD19, CD20, and CD10, but not BCL6 or MTA‐3. Pax5 was downregulated and full plasma cell morphology and phenotype were acquired by PRDM1+, nuclear cREL−, pre‐plasma cells upon exit from the germinal centre. Activated extrafollicular B‐cells (CD30+, Pax5+) were largely PRDM1−. PRDM1 was also absent in tissue histiocytes and the majority of resting T‐cells and S‐100+ antigen‐presenting cells. PRDM1 and CD138 were expressed simultaneously in human lymphomas with plasma cell differentiation, but not in marginal zone lymphomas or chronic lymphocytic leukaemias. A minority of diffuse large B‐cell lymphomas expressed PRDM1 and Hodgkin lymphomas were largely PRDM1−. Infiltrating T‐cells in PRDM1− B‐cell lymphomas expressed PRDM1. In conclusion, PRDM1 staining is a reliable and informative assay to define plasma cell commitment and differentiation in human normal and neoplastic B‐cell lineages. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[1]  Y. Tu,et al.  Cattoretti and Riccardo Dalla-favera Tracking Cd40 Signaling during Germinal Center Development , 2022 .

[2]  H. Stein,et al.  Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. , 2004, Blood.

[3]  Jhagvaral Hasbold,et al.  Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression , 2004, The Journal of experimental medicine.

[4]  David L. Jaye,et al.  MTA3 and the Mi-2/NuRD Complex Regulate Cell Fate during B Lymphocyte Differentiation , 2004, Cell.

[5]  L. Staudt,et al.  Direct Repression of prdm1 by Bcl-6 Inhibits Plasmacytic Differentiation1 , 2004, The Journal of Immunology.

[6]  L. Staudt,et al.  XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. , 2004, Immunity.

[7]  K. Makar,et al.  Sounds of a silent Blimp-1 , 2004, Nature Immunology.

[8]  Nallasivam Palanisamy,et al.  Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. , 2004, Blood.

[9]  Lin Yang,et al.  Novel relational database for tissue microarray analysis. , 2009, Archives of pathology & laboratory medicine.

[10]  L. Pasqualucci,et al.  Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). , 2003, Blood.

[11]  K. Calame,et al.  Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. , 2003, Immunity.

[12]  A. Mantovani,et al.  The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. , 2003, Blood.

[13]  E. Jaffe Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues , 2003 .

[14]  Gregory H Underhill,et al.  Gene expression profiling reveals a highly specialized genetic program of plasma cells. , 2003, Blood.

[15]  Andrea Califano,et al.  Transcriptional analysis of the B cell germinal center reaction , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Andrea Califano,et al.  Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. , 2003, The Journal of clinical investigation.

[17]  V. Diehl,et al.  Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. , 2003, Blood.

[18]  F. Zhan,et al.  Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development. , 2003, Blood.

[19]  Martin Zenke,et al.  Nuclear Factor κB–dependent Gene Expression Profiling of Hodgkin's Disease Tumor Cells, Pathogenetic Significance, and Link to Constitutive Signal Transducer and Activator of Transcription 5a Activity , 2002, The Journal of experimental medicine.

[20]  K. Calame,et al.  The dynamic expression pattern of B lymphocyte induced maturation protein-1 (Blimp-1) during mouse embryonic development , 2002, Mechanisms of Development.

[21]  H. Stein,et al.  Aberrantly expressed c‐Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF‐κB , 2002, The EMBO journal.

[22]  M. Busslinger,et al.  Reversion of B Cell Commitment upon Loss of Pax5 Expression , 2002, Science.

[23]  Kuo-I Lin,et al.  Blimp-1-Dependent Repression of Pax-5 Is Required for Differentiation of B Cells to Immunoglobulin M-Secreting Plasma Cells , 2002, Molecular and Cellular Biology.

[24]  Liming Yang,et al.  Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. , 2002, Immunity.

[25]  Donna Neuberg,et al.  Center B Cells Using Cdna Arrays Gene Expression Profiling of Follicular Lymphoma and Normal Germinal , 2002 .

[26]  Y. Tu,et al.  Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells , 2001, The Journal of experimental medicine.

[27]  K. Calame Immunology: End game for B cells , 2001, Nature.

[28]  I. Berberich,et al.  Blimp‐1 over‐expression abrogates IL‐4‐ and CD40‐mediated suppression of terminal B cell differentiation but arrests isotype switching , 2001, European journal of immunology.

[29]  N. Palanisamy,et al.  IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy. , 2001, Immunity.

[30]  G. Cattoretti,et al.  Commitment of B Lymphocytes to a Plasma Cell Fate Is Associated with Blimp-1 Expression In Vivo1 , 2000, The Journal of Immunology.

[31]  K. Calame,et al.  BLIMP-1: trigger for differentiation of myeloid lineage , 2000, Nature Immunology.

[32]  H Stein,et al.  A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. , 2000, Blood.

[33]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[34]  K. Rajewsky,et al.  Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. , 2000, Blood.

[35]  G. Lenz,et al.  Frequent expression of the B-cell-specific activator protein in Reed-Sternberg cells of classical Hodgkin's disease provides further evidence for its B-cell origin. , 1999, Blood.

[36]  P G Soro,et al.  Differential involvement of the transcription factor Blimp-1 in T cell-independent and -dependent B cell differentiation to plasma cells. , 1999, Journal of immunology.

[37]  Rodney T. Miller,et al.  Blocking of Endogenous Avidin-Binding Activity in Immunohistochemistry: The Use of Skim Milk as an Economical and Effective Substitute for Commercial Biotin Solutions , 1999 .

[38]  Christoph Schaniel,et al.  Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells , 1998, The Journal of experimental medicine.

[39]  I. Weissman,et al.  Arrest of B lymphocyte terminal differentiation by CD40 signaling: mechanism for lack of antibody-secreting cells in germinal centers. , 1998, Immunity.

[40]  K. Calame,et al.  Repression of c-myc transcription by Blimp-1, an inducer of terminal B cell differentiation. , 1997, Science.

[41]  Rodney T. Miller,et al.  Blocking of Endogenous Avidin-Binding Activity in Immunohistochemistry: The Use of Egg Whites , 1997 .

[42]  É. Mezey,et al.  Immunohistochemical signal amplification by catalyzed reporter deposition and its application in double immunostaining. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[43]  K. Rajewsky,et al.  Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells , 1996, The Journal of experimental medicine.

[44]  G Janossy,et al.  Quantitative analysis of leukocyte membrane antigen expression: normal adult values. , 1996, Cytometry.

[45]  K. Offit,et al.  BCL-6 protein is expressed in germinal-center B cells. , 1995, Blood.

[46]  E. Kremmer,et al.  B‐cell proliferation and induction of early G1‐regulating proteins by Epstein‐Barr virus mutants conditional for EBNA2. , 1995, The EMBO journal.

[47]  Johannes Gerdes,et al.  Antigen unmasking on formalin‐fixed, paraffin‐embedded tissue sections , 1993, The Journal of pathology.

[48]  Johannes Gerdes,et al.  Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections , 1992, The Journal of pathology.

[49]  E. Roldán,et al.  Terminal differentiation of human bone marrow cells capable of spontaneous and high‐rate immunoglobulin secretion: Role of bone marrow stromal cells and interleukin 6 , 1991, European journal of immunology.

[50]  F. Rilke,et al.  Terminal deoxynucleotidyl transferase‐positive B cell precursors in fetal lymph nodes and extrahemopoietic tissues , 1989, European journal of immunology.

[51]  K. Lennert,et al.  The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. , 1985, Blood.