Activation and negative selection of functionally distinct subsets of antibody-secreting cells by influenza hemagglutinin as a viral and a neo-self antigen.
Activation and negative selection of functionally distinct subsets of antibody-secreting cells by influenza hemagglutinin as a viral and a neo-self antigen.
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DOI：
10.1084/jem.183.1.13
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Stark SE
中科院分区：
文献类型：
--
作者：
Caton AJ;Swartzentruber JR;Kuhl AL;Carding SR;Stark SE
我们比较了表达流感病毒PR 8血凝素（PR 8 HA）作为膜结合新自身抗原的转基因小鼠（HA 104小鼠）与非转基因（非Tg）小鼠在PR 8病毒初次免疫后产生HA特异性B细胞应答的能力。HA特异性分泌IgM的B细胞在HA 104和非Tg小鼠中以相似的频率诱导。此外，在来自HA 104小鼠的HA特异性IgM杂交瘤中鉴定了作为BALB/c小鼠抗HA免疫应答特征的B细胞克隆型（C4）。然而，HA特异性IgG分泌B细胞亚群在非Tg小鼠中初次病毒免疫后迅速增加，在HA 104小鼠中显著减少。同样，在非Tg小鼠初次免疫后产生的HA特异性IgG杂交瘤中占优势的B细胞克隆型（C12）在来自HA 104小鼠的杂交瘤中以大大降低的频率存在。因为HA特异性的、分泌IgG的B细胞是由HA 104小鼠响应于在B细胞抗原位点中含有氨基酸互换的突变体HA而产生的，所以我们得出结论，这些PR 8 HA特异性的、分泌IgG的B细胞由于其对新自身PR 8 HA的特异性而在HA 104小鼠中被阴性选择。这些发现表明，在非Tg小鼠中显示不同表型潜能的HA特异性B细胞在其对阴性选择的敏感性方面也与HA 104小鼠的原代B细胞库不同：在非Tg小鼠中活化后经历快速分化成为HA特异性IgG抗体分泌细胞（ASC）的B细胞亚组在HA 104小鼠中被阴性选择。相比之下，产生HA特异性、分泌IgM的ASC的亚群持续存在于HA 104小鼠的主要库中，并且可以通过病毒免疫激活。
We have compared transgenic mice that express the influenza virus PR8 hemagglutinin (PR8 HA) as a membrane-bound neo-self antigen (HA104 mice) with nontransgenic (non-Tg) mice for their ability to generate HA- specific B cell responses after primary immunization with PR8 virus. HA- specific, IgM-secreting B cells were induced with similar frequencies in HA104 and non-Tg mice. In addition, a B cell clonotype (C4) that is characteristic of anti-HA immune responses of BALB/c mice was identified among HA-specific IgM hybridomas from HA104 mice. A subset of HA-specific, IgG-secreting B cells that arises rapidly after primary virus immunization in non-Tg mice, however, was substantially reduced in HA104 mice. Likewise, a B cell clonotype (C12) that dominates HA- specific IgG hybridomas generated after primary immunization of non-Tg mice was present at greatly reduced frequencies among hybridomas from HA104 mice. Because HA-specific, IgG-secreting B cells were generated by HA104 mice in response to a mutant HA containing an amino acid interchange in a B cell antigenic site, we conclude that these PR8 HA- specific, IgG-secreting B cells are negatively selected in HA104 mice as a result of their specificity for the neo-self PR8 HA. The findings demonstrate that HA-specific B cells that display distinct phenotypic potentials in non-Tg mice also differ in their susceptibility to negative selection from the primary B cell repertoire of HA104 mice: a subset of B cells that undergo rapid differentiation to become HA- specific IgG antibody-secreting cells (ASC) after activation in non-Tg mice is negatively selected in HA104 mice. By contrast, a subset that gives rise to HA-specific, IgM-secreting ASC persists in the primary repertoire of HA104 mice and can be activated by virus immunization.
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DOI：
10.1084/jem.172.1.371
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carmack CE;Shinton SA;Hayakawa K;Hardy RR
通讯作者：
Hardy RR
影响因子：
56.9
作者：
ADELSTEIN, S;PRITCHARDBRISCOE, H;GOODNOW, CC
通讯作者：
GOODNOW, CC
影响因子：
64.5
作者：
FITZGERALD, M;SHENK, T
通讯作者：
SHENK, T
影响因子：
2.2
作者：
CZERKINSKY, CC;NILSSON, LA;TARKOWSKI, A
通讯作者：
TARKOWSKI, A
影响因子：
64.5
作者：
BEREK, C;BERGER, A;APEL, M
通讯作者：
APEL, M