Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies.
Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies.
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DOI：
10.1016/j.jbc.2022.102468
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发表时间：
2022-10
影响因子：
4.8
通讯作者：
Gildersleeve, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Temme, J. Sebastian;Crainic, Jennifer A.;Walker, Laura M.;Yang, Weizhun;Tan, Zibin;Huang, Xuefei;Gildersleeve, Jeffrey C.
The immune system produces a diverse collection of antiglycan antibodies that are critical for host defense. At present, however, we know very little about the binding properties, origins, and sequences of these antibodies because of a lack of access to a variety of defined individual antibodies. To address this challenge, we used a glycan microarray with over 800 different components to screen a panel of 516 human monoclonal antibodies that had been randomly cloned from different B-cell subsets originating from healthy human subjects. We obtained 26 antiglycan antibodies, most of which bound microbial carbohydrates. The majority of the antiglycan antibodies identified in the screen displayed selective binding for specific glycan motifs on our array and lacked polyreactivity. We found that antiglycan antibodies were about twice as likely than expected to originate from IgG+ memory B cells, whereas none were isolated from naïve, early emigrant, or immature B cells. Therefore, our results indicate that certain B-cell subsets in our panel are enriched in antiglycan antibodies, and IgG+ memory B cells may be a promising source of such antibodies. Furthermore, some of the newly identified antibodies bound glycans for which there are no reported monoclonal antibodies available, and these may be useful as research tools, diagnostics, or therapeutic agents. Overall, the results provide insight into the types and properties of antiglycan antibodies produced by the human immune system and a framework for the identification of novel antiglycan antibodies in the future.
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