Large-scale Analysis of 2,152 dataset reveals key features of B cell biology and the antibody repertoire

Zhang, Z.; Yang, X.; Wang, M.; Shi, D.; Zhang, Y.; Zeng, H.; Yan, Z.; Lan, C.; Wu, J.; Deng, Y.; Guo, S.; Xu, L.; Ma, C.; Wu, R.; Ou, J.; Liu, C.-j.; Chang, C.; Yang, W.; Zhang, H.; Chen, J.; Qin, L.; Zhou, H.; Bei, J.-X.; Wei, L.; Cao, G.; Yu, X.

doi:10.1101/814590

bioRxiv · 10.1101/814590

Large-scale Analysis of 2,152 dataset reveals key features of B cell biology and the antibody repertoire

Zhang, Z.·Yang, X.·Wang, M.·Shi, D.·Zhang, Y.·Zeng, H.·Yan, Z.·Lan, C.·Wu, J.·Deng, Y.·Guo, S.·Xu, L.·Ma, C.·Wu, R.·Ou, J.·Liu, C.-j.·Chang, C.·Yang, W.·Zhang, H.·Chen, J.·Qin, L.·Zhou, H.·Bei, J.-X.·Wei, L.·Cao, G.·Yu, X.

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Abstract

Antibody repertoire sequencing (Ig-seq) has been widely used in studying humoral responses, with promising results. However, the promise of Ig-seq has not yet been fully realized, and key features of the antibody repertoire remain elusive or controversial. To clarify these key features, we analyzed 2,152 high-quality heavy chain antibody repertoires, representing 582 donors and a total of 360 million clones. Our study revealed that individuals exhibit very similar gene usage patterns for germline V, D, and J genes and that 53 core V genes contribute to more than 99% of the heavy chain repertoire. We further found that genetic background is sufficient but not necessary to determine usage of V, D, and J genes. Although gene usage pattern is not affected by age, we observed a significant sex preference for 24 V genes, 9 D genes and 5 J genes, but found no positional bias for V-D and D-J recombination. In addition, we found that the number of observed clones that were shared between any two repertoires followed a linear model and noted that the mutability of hot/cold spots and single nucleotides within antibody genes suggested a strand-specific somatic hypermutation mechanism. This population-level analysis resolves some critical characteristics of the antibody repertoire and thus may serve as a reference for research aiming to unravel B cell-related biology or diseases. The metrics revealed here will be of significant value to the large cadre of scientists who study the antibody repertoire.

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Zhang, Z., Yang, X., Wang, M., Shi, D., Zhang, Y., Zeng, H., Yan, Z., Lan, C., Wu, J., Deng, Y., Guo, S., Xu, L., Ma, C., Wu, R., Ou, J., Liu, C.-j., Chang, C., Yang, W., Zhang, H., Chen, J., Qin, L., Zhou, H., Bei, J.-X., Wei, L., Cao, G., Yu, X.. 2019-10-22. Large-scale Analysis of 2,152 dataset reveals key features of B cell biology and the antibody repertoire. https://doi.org/10.1101/814590

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