BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation

被引:119
作者
Eckl-Dorna, Julia [1 ]
Batista, Facundo D. [1 ]
机构
[1] Lincolns Inn Fields Labs, Canc Res UK London Res Inst, Lymphocyte Interact Lab, London WC2A 3PX, England
关键词
TOLL-LIKE RECEPTORS; CLASS SWITCH RECOMBINATION; ANTIBODY-RESPONSES; CLASS-II; IN-VIVO; GERMINAL-CENTERS; TRANSGENIC MICE; BACTERIAL-DNA; T-CELLS; CPG-DNA;
D O I
10.1182/blood-2008-10-185421
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The activation of Toll-like receptor 9 (TLR9) expressed within B cells is associated with enhanced humoral immunity. However the role of TLR9 in the stimulation of B-cell responses, and more specifically in shaping the outcome of B-cell differentiation, remains unclear. Here, we observed that immunization with the TLR9 agonist CpG linked to protein antigen gave rise to enhanced production of antigen-specific class-switched antibodies in vivo. Unlike dendritic cells, B cells are unable to acquire these conjugates by macropinocytosis and instead depend on uptake through a signaling-competent B-cell receptor (BCR), provided the overall BCR-antigen avidity exceeds a defined threshold. The resultant stimulation of intrinsic TLR9 leads to enhanced antigen-specific B-cell proliferation and differentiation to form extrafollicular plasma cells. Thus, the direct conjugation of antigen and CpG reveals a mechanism that may operate during the initiation of primary immune responses, and may prove useful as a strategy for the design of adjuvants suitable for vaccinations. (Blood. 2009;113:3969-3977)
引用
收藏
页码:3969 / 3977
页数:9
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