title: AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies.
abstract: Neoplastic transformation of mature B cells can be triggered by class-switch recombination of the immunoglobulin gene, which aberrantly targets a protooncogene and promotes translocation. Class-switch recombination is initiated by the B-cell-specific protein activation-induced cytidine deaminase (AID). Using immunohistochemistry with a newly generated monoclonal antibody and quantitative reverse-transcription-polymerase chain reaction (RT-PCR) on microdissected tissue from lymph node, tonsil, and thymus, we demonstrate that AID expression is found in secondary lymphoid organs outside germinal centers and in the thymic medulla at substantial levels. This is accompanied by the presence of circle transcripts, indicating class-switch recombination to be active at these sites. The dominant AID-expressing cell population outside germinal centers displays cytomorphologic properties corresponding to those that define the recently characterized interfollicular large B-cell subset. These findings indicate that interfollicular large B cells and AID-expressing B lymphocytes of the thymic medulla could give rise to mature B-cell malignancies.
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Moldenhauer
authors.forename: Sergey W
authors.initials: SW
authors.lastname: Popov
authors.forename: Beate
authors.initials: B
authors.lastname: Wotschke
authors.forename: Silke
authors.initials: S
authors.lastname: Brüderlein
authors.forename: Petra
authors.initials: P
authors.lastname: Riedl
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fissolo
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schirmbeck
authors.forename: Olga
authors.initials: O
authors.lastname: Ritz
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Frank
authors.initials: F
authors.lastname: Leithäuser
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching; D007150:Immunohistochemistry; D015448:Leukemia, B-Cell / Q000209:etiology / Q000473:pathology*; D008221:Lymphoid Tissue / Q000166:cytology*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase