Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.,Journal of Experimental Medicine

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Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-07-25 , DOI: 10.1084/jem.20190164
Tara Bancroft ₁ , Blair L DeBuysscher ₁ , Connor Weidle ₁ , Allison Schwartz ₁ , Abigail Wall ₁ , Matthew D Gray ₁ , Junli Feng ₁ , Holly R Steach ₁ , Kristin S Fitzpatrick ₁ , Mesfin M Gewe ₂ , Patrick D Skog ₃ , Colleen Doyle-Cooper ₃ , Takayuki Ota ₃ , Roland K Strong ₁ , David Nemazee ₃ , Marie Pancera ₁ , Leonidas Stamatatos _{4,

5} , Andrew T McGuire _{4,

5} , Justin J Taylor _{4,

5,

6}

Affiliation

Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.

中文翻译：

使用抗独特型检测和激活HIV广泛中和抗体前体B细胞。

尽管诱导了与目标病原体结合的抗体，但许多经过测试的疫苗仍无法提供针对疾病的保护。鉴于此，合理设计的亚基疫苗引起了人们的极大兴趣，这些亚基疫苗将抗体应答引导至保护性表位。在这里，我们制备了一组抗独特型抗体，能够特异性识别广泛中和抗体b12（iglb12）的人类免疫缺陷病毒1（HIV-1）的推断种系。我们确定了两种与iglb12结合的抗独特型的晶体结构，并使用这些抗独特型来鉴定表达与iglb12相似的B细胞受体的罕见幼稚人类B细胞。用这种抗独特型的多聚体形式免疫后，会在体内诱导表达iglb12重链的转基因鼠B细胞增殖，尽管该人群中存在缺失和无能为力。总之，我们的数据表明抗独特型是研究和诱导潜在保护性抗体的有价值的工具。

更新日期：2019-10-07

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