全长单细胞 BCR 测序与 RNA 测序相结合揭示了对肺炎球菌疫苗接种的趋同反应。

Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to pneumococcal vaccination.

机构信息

Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.

Department of Chemical Engineering, MIT, Cambridge, MA, USA.

出版信息

Commun Biol. 2024 Sep 28;7(1):1208. doi: 10.1038/s42003-024-06823-0.

Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3'-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3'-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination.

单细胞 RNA 测序（scRNA-seq）可以从单个细胞中解析转录特征，但能够解析 B 细胞受体（BCR）可变区的 scRNA-seq 技术仍然有限，特别是来自广泛使用的 3'-条形码文库。在这里，我们报告了一种可以从 3'-条形码 scRNA-seq 文库中恢复 BCR 的配对全长可变区序列的方法。我们首先验证了这种方法（B3E-seq）可以产生准确的全长 BCR 序列。然后，我们将该方法应用于五种婴儿恒河猴对肺炎链球菌血清型 3（ST3）荚膜多糖的糖缀合物疫苗引发的 B 细胞反应进行分析。我们确定了与 ST3 抗原特异性相关的 BCR 特征，这些特征存在于多个接种疫苗的猴子中，表明对疫苗接种有趋同反应。这些结果表明，我们的方法可用于解析 B 细胞库的关键特征，并对疫苗接种引发的抗原特异性反应进行分析。