![]() It has, however, also been demonstrated that the early IgM response can influence the clearance of chronic LCMV infection in the context of transgenic mice expressing virus-neutralizing antibodies ( Seiler et al., 1998). Despite this increase in serum titers against purified virus for both isotypes, the IgG isotype (particularly IgG2c) has been shown to be crucial to resolving persistent LCMV infection ( Barnett et al., 2016). Although both B and CD4+ T cells are dispensable for the resolution of acute LCMV infection, an increase in both IgG and IgM titers against the purified virus has nevertheless been observed in both infection cohorts ( Kräutler et al., 2020). It has been demonstrated that CD8 T cells are necessary for the clearance of acute LCMV infection, whereas the conversion to a follicular response is crucial to resolve persisting LCMV infection via virus-neutralizing antibodies ( Thomsen et al., 1996 Planz et al., 1997 Greczmiel et al., 2017). LCMV is a rodent-borne pathogen that can elicit either an acute (resolved within weeks) or chronic (resolved within months) infection depending on the initial viral strain and dose. To quantify whether the aforementioned parameters can distinguish viral infection cohorts, we utilized both temporally- and spatially-resolved antibody repertoire sequencing data from mice infected with lymphocytic choriomeningitis virus (LCMV) (Kräutler et al., 2020). While previous studies have described and classified infection status based on antibody repertoire sequencing ( Greiff et al., 2015b Emerson et al., 2017), it remains largely unknown how multiple sampling time points, antibody isotype, and organ selection impacts these fingerprints, especially in the context of viral infection. Furthermore, peripheral blood heavily biases the cellular composition to naïve B cells of the IgM isotype, as seen with single-cell sequencing experiments ( Horns et al., 2020). This implicitly enables time-resolved sampling of the antibody repertoire within the same host over time, despite sacrificing spatial and physiological resolution from repertoires across multiple organs. In human patients, however, most antibody repertoire sequencing experiments are limited to circulating B cells in the peripheral blood ( Doria-Rose et al., 2014 Jackson et al., 2014 Tsioris et al., 2015 Wu et al., 2015 Vander Heiden et al., 2017). Immunologically intuitive metrics, such as sequence diversity, clonal expansion, and germline gene usage have been routinely employed to quantify antibody repertoire fingerprints between different vaccine and infection conditions, based entirely on the antibody repertoire ( Jiang et al., 2013 Jackson et al., 2014 Greiff et al., 2017). Immune-status profiling demands sufficient sensitivity and accuracy to provide correct diagnoses given the unquantifiable antigens experienced by an individual ( Robinson, 2014). The cost and time of sequencing an individual's antibody repertoire has dramatically decreased over the past decade, resulting in attempts to infer disease status based on antibody repertoire sequencing ( Greiff et al., 2015a). The possibility of personalized medicine is becoming increasingly possible due to the revolution in high-throughput sequencing (HTS) technologies ( Georgiou et al., 2014 Miho et al., 2018 Brown et al., 2019). Our findings, however, revealed mouse-specific repertoire fingerprints between the blood and PC repertoires irrespective of infection status. ![]() ![]() Despite previously reported serum alterations between acute and chronic infection, IgM repertoire signatures based on clonal diversity metrics, public clones, network, and phylogenetic analysis were largely unable to distinguish infection cohorts. Therefore, we compared the IgM repertoires from both blood and bone marrow (BM) plasma cells (PCs) following acute or chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-resident B cells in the setting of viral infection remains largely uncharacterized. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. 3Department of Immunology, University of Oslo, Oslo, NorwayĪntibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system.2Department of Biosystems and Engineering, ETH Zurich, Basel, Switzerland.1Institute of Microbiology, ETH Zurich, Zurich, Switzerland.Alexander Yermanos 1,2 *, Nike Julia Kräutler 1, Alessandro Pedrioli 1, Ulrike Menzel 2, Victor Greiff 3, Tanja Stadler 2, Annette Oxenius 1 and Sai T.
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