B Cell Selection and Affinity Maturation During an Antibody Response in the Mouse with Limited B Cell Diversity1
B Cell Selection and Affinity Maturation During an Antibody Response in the Mouse with Limited B Cell Diversity1
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B 细胞多样性有限的小鼠抗体反应期间的 B 细胞选择和亲和力成熟1
作者：
N. Kanayama;T. Kimoto;K. Todo;Y. Nishikawa;M. Hikida;M. Magari;M. Cascalho;H. Ohmori
准单克隆小鼠具有有限的B细胞多样性，其主要（约80%）B细胞Ag受体由敲入VH 17.2.25（VHT）编码的H链和λ1或λ2 L链组成，因此对4-羟基-3-硝基苯乙酰具有特异性。发现对硝基苯乙酰基（pNP）是硝基苯乙酰基的低亲和力类似物。我们通过分析从用这种低亲和力Ag免疫的准单克隆小鼠获得的mAb来检查抗pNP IgG的亲和力成熟。结果表明：（1）VHT/λ1和VHT/λ2 IgM的产生量相同，但VHT/λ2 IgG几乎只对pNP发生亲和力成熟。2)VHT的互补决定区3（T313 A）的常见突变主要有助于产生pNP的特异性。3)由于突变的VHT编码的γ链可在中国仓鼠卵巢细胞中形成携带λ1的IgG，因此VHT/λ1抗pNP IgG的明显缺失可能不是由于γ链和λ1链之间的不相容性，而是由于VHT/λ1 B细胞对pNP的亲和力比VHT/λ2 B细胞低50- 100倍。4)有趣的是，分离出了一种pNP特异性IgM mAb，其具有包括T313 A在内的共同突变，具有高亲和力抗pNP IgG，这表明在同种型转换之前可能发生部分超突变与阳性选择。因此，即使弱的B细胞受体结合也可以引发IgM应答，而只有接收到比阈值强的信号的B细胞可以被定向于亲和力成熟过程。
The quasi-monoclonal mouse has limited B cell diversity, whose major (∼80%) B cell Ag receptors are comprised of the knockin VH 17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain, thereby being specific for 4-hydroxy-3-nitrophenylacetyl. The p-nitrophenylacetyl (pNP) was found to be a low affinity analog of nitrophenylacetyl. We examined affinity maturation of anti-pNP IgG by analyzing mAbs obtained from quasi-monoclonal mice that were immunized with this low affinity Ag. The results are: 1) Although VHT/λ1 and VHT/λ2 IgM were equally produced, VHT/λ2 IgG almost exclusively underwent affinity maturation toward pNP. 2) A common mutation in complementarity-determining region 3 of VHT (T313A) mainly contributed to generating the specificity for pNP. 3) Because mutated VHT-encoded γ-chains could form λ1-bearing IgG in Chinese hamster ovary cells, apparent absence of VHT/λ1 anti-pNP IgG may not be due to the incompatibility between the γ-chains and the λ1-chain, but may be explained by the fact that VHT/λ1 B cells showed 50- to 100-fold lower affinity for pNP than VHT/λ2 B cells. 4) Interestingly, a pNP-specific IgM mAb that shared common mutations including T313A with high affinity anti-pNP IgG was isolated, suggesting that a part of hypermutation coupled with positive selection can occur before isotype switching. Thus, even weak B cell receptor engagement can elicit an IgM response, whereas only B cells that received signals stronger than a threshold may be committed to an affinity maturation process.
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抗体亲和力成熟中的超突变。
影响因子：
7
作者：
Wabl,M;Cascalho,M;Steinberg,C
通讯作者：
Steinberg,C
准单克隆小鼠超选择 B 细胞中的 VH 基因替换。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cascalho,M;Wong,J;Wabl,M
通讯作者：
Wabl,M
影响因子：
32.4
作者：
Furukawa, K;Akasako-Furukawa, A;Azuma, T
通讯作者：
Azuma, T
影响因子：
16.8
作者：
Tew, JG;Wu, JH;Qin, DH
通讯作者：
Qin, DH