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.
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, CDC
;
Ansel, KM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Ansel, KM
;
Low, C
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Low, C
;
Lesley, R
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Lesley, R
;
Tamamura, H
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Tamamura, H
;
论文数: 引用数:
h-index:
机构:
Fujii, N
;
Cyster, JG
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, Christopher D. C.
;
Okada, Takaharu
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Okada, Takaharu
;
Cyster, Jason G.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, Christopher D. C.
;
Okada, Takaharu
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Okada, Takaharu
;
Tang, H. Lucy
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Tang, H. Lucy
;
Cyster, Jason G.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, CDC
;
Ansel, KM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Ansel, KM
;
Low, C
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Low, C
;
Lesley, R
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Lesley, R
;
Tamamura, H
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Tamamura, H
;
论文数: 引用数:
h-index:
机构:
Fujii, N
;
Cyster, JG
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, Christopher D. C.
;
Okada, Takaharu
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Okada, Takaharu
;
Cyster, Jason G.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Allen, Christopher D. C.
;
Okada, Takaharu
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Okada, Takaharu
;
Tang, H. Lucy
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Tang, H. Lucy
;
Cyster, Jason G.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA