Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis

被引:208
作者
Horcher, M [1 ]
Souabni, A [1 ]
Busslinger, M [1 ]
机构
[1] Res Inst Mol Pathol, Vienna Bioctr, A-1030 Vienna, Austria
关键词
D O I
10.1016/S1074-7613(01)00153-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The a lineage commitment factor Pax5 (BSAP) is expressed throughout B cell development. To investigate its late function, we generated a mouse strain carrying a flexed Pax5 allele that was conditionally inactivated by CD19-cre or Mx-cre expression. Pax5 deletion resulted in the preferential loss of mature B cells, inefficient lymphoblast formation, and reduced serum IgG levels. Mature B cells radically changed their gene expression pattern in response to Pax5 inactivation. Most B cell antigens were downregulated on the cell surface, and the transcription of B cell-specific genes was decreased, whereas the expression of non-B lymphoid genes was activated in Pax5-deficient B cells. These data demonstrate that Pax5 is essential for maintaining the identity and function of B cells during late B lymphopoiesis.
引用
收藏
页码:779 / 790
页数:12
相关论文
共 48 条
[1]   PAX-5 ENCODES THE TRANSCRIPTION FACTOR BSAP AND IS EXPRESSED IN LYMPHOCYTES-B, THE DEVELOPING CNS, AND ADULT TESTIS [J].
ADAMS, B ;
DORFLER, P ;
AGUZZI, A ;
KOZMIK, Z ;
URBANEK, P ;
MAURERFOGY, I ;
BUSSLINGER, M .
GENES & DEVELOPMENT, 1992, 6 (09) :1589-1607
[2]   Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination [J].
Betz, UAK ;
Vosshenrich, CAJ ;
Rajewsky, K ;
Muller, W .
CURRENT BIOLOGY, 1996, 6 (10) :1307-1316
[3]   Deregulation of PAX-5 by translocation of the E mu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma [J].
Busslinger, M ;
Klix, N ;
Pfeffer, P ;
Graninger, PG ;
Kozmik, Z .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :6129-6134
[4]  
Busslinger Meinrad, 1998, P83
[5]   STRUCTURE OF GENES FOR MEMBRANE AND SECRETED MURINE IGD HEAVY-CHAINS [J].
CHENG, HL ;
BLATTNER, FR ;
FITZMAURICE, L ;
MUSHINSKI, JF ;
TUCKER, PW .
NATURE, 1982, 296 (5856) :410-415
[6]   DNA-SEQUENCE RECOGNITION BY PAX PROTEINS - BIPARTITE STRUCTURE OF THE PAIRED DOMAIN AND ITS BINDING-SITE [J].
CZERNY, T ;
SCHAFFNER, G ;
BUSSLINGER, M .
GENES & DEVELOPMENT, 1993, 7 (10) :2048-2061
[7]   Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family [J].
Eberhard, D ;
Jiménez, G ;
Heavey, B ;
Busslinger, M .
EMBO JOURNAL, 2000, 19 (10) :2292-2303
[8]   BLNK: a central linker protein in B cell activation [J].
Fu, C ;
Turck, CW ;
Kurosaki, T ;
Chan, AC .
IMMUNITY, 1998, 9 (01) :93-103
[9]   The B cell-restricted adaptor BASH is required for normal development and antigen receptor-mediated activation of B cells [J].
Hayashi, K ;
Nittono, R ;
Okamoto, N ;
Tsuji, S ;
Hara, Y ;
Goitsuka, R ;
Kitamura, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (06) :2755-2760
[10]   B cell differentiation and isotype switching is related to division cycle number [J].
Hodgkin, PD ;
Lee, JH ;
Lyons, AB .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (01) :277-281