Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3-and complement receptor 2-deficient mice

Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3-and complement receptor 2-deficient mice
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DOI:
10.4049/jimmunol.170.1.84
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发表时间:
2003-01-01
影响因子:
4.4
通讯作者:
Kasper, DL
Kasper, DL
中科院分区:
医学2区
文献类型:
--
作者:
Pozdnyakova, O;Guttormsen, HK;Kasper, DL

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B族链球菌(GBS)是引起新生儿严重感染的主要细菌。对GBS的保护性免疫由针对生物体的荚膜多糖Ag的特异性Ab介导。为了检测补体在对III型GBS荚膜多糖(III-PS)的体液免疫应答中的作用,将C3或CD 21/CD 35缺陷的小鼠(即,补体受体1和2; CR 1/CR2)用III-PS免疫。缺乏C3或Cr2的小鼠对HI-PS的初级免疫应答受损。缺陷性应答的特征在于IgM水平低和缺乏从IgM到IgG Ab生产的同种型转换。与野生型小鼠相比,C3-和Cr2-缺陷小鼠表现出降低的生发中心内的滤泡树突状细胞的III-PS的摄取和受损的III-PS的边缘区B细胞的本地化。边缘区B细胞对荚膜多糖的补体依赖性摄取似乎是对III-PS的有效免疫应答所必需的。野生型小鼠的正常免疫应答可能需要将多糖定位于边缘区B细胞,随后将Ag转移至滤泡树突状细胞。
Group B Streptococcus (GBS) is the foremost bacterial cause of serious neonatal infections. Protective immunity to GBS is mediated by specific Abs to the organism's capsular polysaccharide Ags. To examine the role of complement in the humoral immune response to type III GBS capsular polysaccharide (III-PS), mice deficient in C3 or in CD21/CD35 (i.e., complement receptors 1 and 2; CR1/CR2) were immunized with III-PS. Mice deficient in C3 or Cr2 had an impaired primary immune response to HI-PS. The defective response was characterized by low IgM levels and the lack of an isotype switch from IgM to IgG Ab production. Compared with wild-type mice, C3- and Cr2-deficient mice exhibited decreased uptake of III-PS by follicular dendritic cells within the germinal centers and impaired localization of III-PS to the marginal zone B cells. Complement-dependent uptake of capsular polysaccharide by marginal zone B cells appears necessary for an effective immune response to III-PS. The normal immune response in wild-type mice may require localization of polysaccharide to marginal zone B cells with subsequent transfer of the Ag to follicular dendritic cells.