AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies.
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.
Moldenhauer
Gerhard
G
Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.
Popov
Sergey W
SW
Wotschke
Beate
B
Brüderlein
Silke
S
Riedl
Petra
P
Fissolo
Nicolas
N
Schirmbeck
Reinhold
R
Ritz
Olga
O
Möller
Peter
P
Leithäuser
Frank
F
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)
D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase