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Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2167-2172
RAPID COMMUNICATION
Nonimmunoglobulin Gene Hypermutation in Germinal Center B Cells
Huai-Zheng Peng,
Ming-Qing Du,
Athanasios Koulis,
Antonella Aiello,
Ahmet Dogan,
Lang-Xing Pan, and
Peter G. Isaacson
From the Department of Histopathology, University College London
Medical School, London, UK; and Divisione Di Anatomia Patologica,
Istituto Nazionale Tumori, Milano, Italy.
Somatic hypermutation is the most critical mechanism underlying the
diversification of Ig genes. Although mutation occurs specifically in B
cells during the germinal center reaction, it remains a matter of
debate whether the mutation machinery also targets non-Ig genes. We
have studied mutations in the 5' noncoding region of the Bcl6 gene in
different subtypes of lymphomas. We found frequent hypermutation in
follicular lymphoma (25 of 59 = 42%) (germinal center cell origin)
and mucosa-associated lymphoid tissue (MALT) lymphoma (19 of
45 = 42%) (postgerminal center), but only occasionally in mantle
cell lymphoma (1 of 21 = 4.8%) (pregerminal center). Most
mutations were outside the motifs potentially important for
transcription, suggesting they were not important in
lymphomagenesis but may, like Ig mutation, represent an inherent feature of the lymphoma precursor cells. Therefore, we investigated their normal cell counterparts microdissected from a reactive tonsil.
Bcl6 mutation was found in 13 of 24 (54%) clones from the germinal
centre but only in 1 of 24 (4%) clones from the naive B cells of the
mantle zone. The frequency, distribution, and nature of these mutations
were similar to those resulting from the Ig hypermutation process. The
results show unequivocal evidence of non-Ig gene hypermutation in
germinal center B cells and provide fresh insights into the process of
hypermutation and lymphomagenesis.
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