Induction of in vivo antipolysaccharide immunoglobulin responses to intact Streptococcus pneumoniae is more heavily dependent on Btk-mediated B-cell receptor signaling than antiprotein responses

Induction of in vivo antipolysaccharide immunoglobulin responses to intact Streptococcus pneumoniae is more heavily dependent on Btk-mediated B-cell receptor signaling than antiprotein responses
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DOI:
10.1128/iai.74.2.1419-1424.2006
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发表时间:
2006-02-01
影响因子:
3.1
通讯作者:
Snapper, CM
Snapper, CM
中科院分区:
医学2区
文献类型:
--
作者:
Khan, AQ;Sen, G;Snapper, CM

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Btk依赖性B细胞受体(BCR)信号传导在体内诱导抗多糖(抗PS)和抗蛋白免疫球蛋白(IG)对完整细胞外细菌应答中的相对作用尚不清楚。Btk(低)小鼠表现出减少的BCR信号,但在很大程度上恢复B细胞发育。用完整肺炎链球菌免疫的Btk(低)小鼠引起降低的抗PS但正常的抗蛋白IG应答。用PS-蛋白缀合物在盐水中免疫Btk(低)小鼠导致抗PS而不是抗蛋白应答中的甚至更深刻的缺陷,其通过使用含CpG的寡脱氧核苷酸作为佐剂而在很大程度上恢复。这些数据表明,Btk介导的BCR信号生理抗PS相对于抗蛋白反应的依赖性更大,以及存在一个补偿Toll样受体介导的信号通路,自然触发的完整的细菌病原体。
The relative role of Btk-dependent B-cell receptor (BCR) signaling in the induction of antipolysaccharide (anti-PS) and antiprotein immunoglobulin (Ig) responses to an intact extracellular bacterium in vivo is unknown. Btk(low) mice exhibit reduced BCR signaling but largely restore B-cell development. Btk(low) mice immunized with intact Streptococcus pneumoniae elicit reduced anti-PS but normal antiprotein Ig responses. Immunization of Btk(low) mice with PS-protein conjugate in saline results in an even more profound defect in the anti-PS but not antiprotein response, which is largely restored by use of a CpG-containing oligodeoxynucleotide as an adjuvant. These data demonstrate a greater dependence on Btk-mediated BCR signaling for physiologic anti-PS relative to antiprotein responses, as well as the existence of a compensatory Toll-like-receptor-mediated signaling pathway naturally triggered in response to intact bacterial pathogens.