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However, due to experimental limitations, a comprehensive description of linked genotypic, phenotypic, and antibody repertoire features of plasma cells (gene expression, clonal frequency, virus specificity, and affinity) has been challenging to obtain. To address this, we performed single\u2010cell transcriptome and antibody repertoire sequencing of the murine BM plasma cell population following chronic lymphocytic choriomeningitis virus infection. Our single\u2010cell sequencing approach recovered full\u2010length and paired heavy\u2010 and light\u2010chain sequence information for thousands of plasma cells and enabled us to perform recombinant antibody expression and specificity screening. Antibody repertoire analysis revealed that, relative to protein immunization, chronic infection led to increased levels of clonal expansion, class\u2010switching, and somatic variants. Furthermore, antibodies from the highly expanded and class\u2010switched (IgG) plasma cells were found to be specific for multiple viral antigens and a subset of clones exhibited cross\u2010reactivity to nonviral and autoantigens. Integrating single\u2010cell transcriptome data with antibody specificity suggested that plasma cell transcriptional phenotype was correlated to viral antigen specificity. Our findings demonstrate that chronic viral infection can induce and sustain plasma cell clonal expansion, combined with significant somatic hypermutation, and can generate cross\u2010reactive antibodies.<\/jats:p>","DOI":"10.1002\/eji.202149331","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T19:43:11Z","timestamp":1635882191000},"page":"297-311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Profiling the specificity of clonally expanded plasma cells during chronic viral infection by single\u2010cell analysis"],"prefix":"10.1002","volume":"52","author":[{"given":"Daniel","family":"Neumeier","sequence":"first","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Pedrioli","sequence":"additional","affiliation":[{"name":"Institute of 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