Absence of immunoglobulin class switch in primary lymphomas of the central nervous system.
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.
Montesinos-Rongen
Manuel
M
Department of Neuropathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Köln, Germany.
Schmitz
Roland
R
Courts
Cornelius
C
Stenzel
Werner
W
Bechtel
Dörte
D
Niedobitek
Gerald
G
Blümcke
Ingmar
I
Reifenberger
Guido
G
von Deimling
Andreas
A
Jungnickel
Berit
B
Wiestler
Otmar D
OD
Küppers
Ralf
R
Deckert
Martina
M
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)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase