The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development

被引:123
作者
Liang, HE
Hsu, LY
Cado, D
Cowell, LG
Kelsoe, G
Schlissel, MS [1 ]
机构
[1] Univ Calif Berkeley, Div Immunol, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD 21205 USA
[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
关键词
D O I
10.1016/S1074-7613(02)00448-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previous in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice. We found that the core-RAG2-containing recombinase complex is selectively defective in catalyzing V-to-DJ rearrangement at the IgH and TCRO loci, resulting in partial developmental blocks in B and T lymphopoiesis. Analysis of recombination intermediates showed defects at the cleavage phase of the reaction. We also observed a reduction in overall recombinase activity in core-RAG2-expressing thymocytes, leading us to suggest that the interaction of a defective recombinase with RSS sequences unique to VH and Vbeta gene segments may underlie the specific V-to-DJ rearrangement defect in core-RAG2 mice.
引用
收藏
页码:639 / 651
页数:13
相关论文
共 42 条
[21]   THE DEFECT IN MURINE SEVERE COMBINED IMMUNE-DEFICIENCY - JOINING OF SIGNAL SEQUENCES BUT NOT CODING SEGMENTS IN V(D)J RECOMBINATION [J].
LIEBER, MR ;
HESSE, JE ;
LEWIS, S ;
BOSMA, GC ;
ROSENBERG, N ;
MIZUUCHI, K ;
BOSMA, MJ ;
GELLERT, M .
CELL, 1988, 55 (01) :7-16
[22]   REGULATION OF V(D)J RECOMBINATION ACTIVATOR PROTEIN RAG-2 BY PHOSPHORYLATION [J].
LIN, WC ;
DESIDERIO, S .
SCIENCE, 1993, 260 (5110) :953-959
[23]   A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination activity [J].
McMahan, CJ ;
Difilippantonio, MJ ;
Rao, N ;
Spanopoulou, E ;
Schatz, DG .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (08) :4544-4552
[24]   A Role for Histone Acetylation in the Developmental Regulation of V(D)J Recombination [J].
McMurry, Michelle Taylor ;
Krangel, Michael S. .
JOURNAL OF IMMUNOLOGY, 2017, 199 (01) :5-8
[25]   RAG1 and RAG2 cooperate in specific binding to the recombination signal sequence in vitro [J].
Mo, XM ;
Bailin, T ;
Sadofsky, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (11) :7025-7031
[26]   Mice with a fluorescent marker for interleukin 2 gene activation [J].
Naramura, M ;
Hu, RJ ;
Gu, H .
IMMUNITY, 1998, 9 (02) :209-216
[27]   Separation-of-function mutants reveal critical roles for RAG2 in both the cleavage and joining steps of V(D)J recombination [J].
Qiu, JX ;
Kale, SB ;
Schultz, HY ;
Roth, DB .
MOLECULAR CELL, 2001, 7 (01) :77-87
[28]   Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a requirement for novel elements in the N-terminus of RAG-1 [J].
Roman, CAJ ;
Cherry, SR ;
Baltimore, D .
IMMUNITY, 1997, 7 (01) :13-24
[29]   DOUBLE-STRAND SIGNAL SEQUENCE BREAKS IN V(D)J RECOMBINATION ARE BLUNT, 5'-PHOSPHORYLATED, RAG-DEPENDENT, AND CELL-CYCLE-REGULATED [J].
SCHLISSEL, M ;
CONSTANTINESCU, A ;
MORROW, T ;
BAXTER, M ;
PENG, A .
GENES & DEVELOPMENT, 1993, 7 (12B) :2520-2532
[30]   The interleukin 7 receptor is required for T cell receptor γ locus accessibility to the V(D)J recombinase [J].
Schlissel, MS ;
Durum, SD ;
Muegge, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (06) :1045-1050