title: Absence of immunoglobulin class switch in primary lymphomas of the central nervous system.
abstract: Primary lymphomas of the central nervous system (PCNSLs) were investigated for their capacity to perform further maturation steps. We studied a series of 11 PCNSLs derived from immunocompetent patients for immunoglobulin (Ig) class switch recombination (CSR) by performing reverse transcriptase-polymerase chain reaction (RT-PCR) for transcripts of Ig constant region gene segments (IGHC). This analysis revealed exclusive transcription of IgM and IgD mRNA in the absence of IgG, IgA, or IgE transcription. This finding was corroborated at the protein level by the immunohistochemical demonstration of IgM on the surface of the tumor cells. The unexpected lack of CSR may be due to internal switch mu region deletions, which were detected in 7 of 11 cases. We also found that expression of activation-induced cytidine deaminase (AID), which is required for CSR and somatic hypermutation, was detectable by RT-PCR in 4 of 10 cases and by immunohistochemistry in one of three cases analyzed. This may indicate that ongoing somatic mutation, which is often observed in PCNSL, could be due to sustained AID expression in a fraction of cases and that intraclonal V gene diversity may occur in other cases at an earlier phase of tumor clone expansion, when AID may have been expressed.
authors.affiliation: Department of Neuropathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Köln, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitz
authors.forename: Cornelius
authors.initials: C
authors.lastname: Courts
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.forename: Dörte
authors.initials: D
authors.lastname: Bechtel
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blümcke
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Berit
authors.initials: B
authors.lastname: Jungnickel
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
mesh_terms: D000328:Adult; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000276:immunology* / Q000378:metabolism; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000096:biosynthesis; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching; D007150:Immunohistochemistry; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase