A role for DRAK2 in the germinal center reaction and the antibody response

被引:10
作者
Al-Qahtani, Ahmed [1 ,2 ]
Xu, Zhenming [1 ,2 ]
Zan, Hong [1 ,2 ]
Walsh, Craig M. [1 ,2 ]
Casali, Paolo [1 ,2 ,3 ]
机构
[1] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Sch Biol Sci, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Sch Med, Dept Med, Irvine, CA 92697 USA
关键词
B cells; antibodies; spleen and germinal centers; molecular biology; transgenic/knockout mice;
D O I
10.1080/08916930802170633
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
DAP-related apoptotic kinase-2 (DRAK2), a death-associated protein kinase family member, is highly expressed in B and T lymphocytes in the human and the mouse. To determine whether DRAK2 plays a role in B-cell activation and differentiation, we analyzed germinal centers (GCs) and the specific antibody response to NP in drak2(-/-) mice immunized with the thymus-dependent (TD) conjugated hapten NP(16)-CGG. In drak2(-/-) mice, spleen GCs were normal in size and morphology, but their number was reduced by as much as 5-fold, as compared to their wild-type littermates. This was not due to a defect in B-cell proliferation, as the BrdU uptake was comparable in DRAK2-deficient and wild-type B cells. Rather, the proportion of apoptotic GC B and T cells in drak2(-/-) mice was significantly higher than that in wild-type control mice, as shown by 7-AAD and terminal deoxynucleotide transferase dUTP nick end labeling ( TUNEL) staining. In drak2(-/-) mice, the generation high affinity IgG antibodies was impaired in spite of the seemingly normal somatic hypermutation and class switch DNA recombination machineries in drak2(-/-) B cells. In NP(16)-CGG-immunized drak2(-/-) mice, T-cell-intrinsic Bcl-xL transgene expression increased the number of GCs and rescued the high affinity IgG response to NP. These findings suggest a novel role for DRAK2 in regulating the GC reaction and the response to TD antigens, perhaps through increased survival of T cells and enhanced B-cell positive selection. They also suggest that DRAK2-deficiency is not involved in regulating intrinsic B-cell apoptosis.
引用
收藏
页码:341 / 352
页数:12
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