The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.
Structural alterations of the promoter region of the BCL-6 proto-oncogene represent the most frequent genetic alteration associated with non-Hodgkin lymphoma, a malignancy often deriving from germinal-centre B cells. The BCL-6 gene encodes a zinc-finger transcriptional repressor normally expressed in both B cells and CD4+ T cells within germinal centres, but its precise function is unknown. We show that mice deficient in BCL-6 displayed normal B-cell, T-cell and lymphoid-organ development but have a selective defect in T-cell-dependent antibody responses. This defect included a complete lack of affinity maturation and was due to the inability of follicular B cells to proliferate and form germinal centres. In addition, BCL-6-deficient mice developed an inflammatory response in multiple organs characterized by infiltrations of eosinophils and IgE-bearing B lymphocytes typical of a Th2-mediated hyperimmune response. Thus, BCL-6 functions as a transcriptional switch that controls germinal centre formation and may also modulate specific T-cell-mediated responses. Altered expression of BCL-6 in lymphoma represents a deregulation of the pathway normally leading to B cell proliferation and germinal centre formation.
Ye
B H
BH
Department of Pathology, Columbia University, New York, New York 10032, USA.
Cattoretti
G
G
Shen
Q
Q
Zhang
J
J
Hawe
N
N
de Waard
R
R
Leung
C
C
Nouri-Shirazi
M
M
Orazi
A
A
Chaganti
R S
RS
Rothman
P
P
Stall
A M
AM
Pandolfi
P P
PP
Dalla-Favera
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001424:Bacterial Infections / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D005854:Germ Cells; D007249:Inflammation / Q000235:genetics*; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D018418:Th2 Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors