TXNIP regulates germinal center generation by suppressing BCL-6 expression.
The detailed mechanism driving the germinal center (GC) reaction to B cell lymphomagenesis has not been clarified. Thioredoxin interacting protein (TXNIP), also known as vitamin D3 up-regulated protein 1 which is an important tumor repressor, is involved in stress responses, redox regulation, and cellular proliferation. Here, we report that TXNIP has a potential role in the formation of GC in peripheral lymphoid organs where B lymphocytes divide rapidly. First, we compared changes in GC from wild type mice and Txnip(-/-) mice. After immunization, Txnip(-/-) mice exhibited higher expression level of BCL-6 and larger percentage of GC B cells with the reduction in antibody production and plasma cell numbers. In addition, Txnip(-/-) spleens had a much larger population which expressed Ki-67, a marker of cell proliferation, in the red pulp border than WT spleens. Furthermore, the expression of BCL-6 was decreased in TXNIP overexpressing cells and elevated in TXNIP deficient cells. Taken together, we conclude that TXNIP may contribute to the formation of GCs after immunization. During this process, TXNIP suppresses BCL-6 expression.
Shao
Yan
Y
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon 305-333, Republic of Korea.
Kim
Sang Yong
SY
Shin
Daesung
D
Kim
Mi Sun
MS
Suh
Hyun-Woo
HW
Piao
Zheng-Hao
ZH
Jeong
Mira
M
Lee
Suk Hyung
SH
Yoon
Suk Ran
SR
Lim
Byung Ho
BH
Kim
Woo-Ho
WH
Ahn
Jeong Keun
JK
Choi
Inpyo
I
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology*; D049109:Cell Proliferation; D015536:Down-Regulation; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000276:immunology*
D002352:Carrier Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C486715:TXNIP protein, human