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Here, we first show that non\u2010circulating B cells obtained from nasal, trachea and lung tissues are numerically and phenotypically distinct from their circulating counterparts. Analysis of single cell transcriptome sequence identified multiple differentially expressed genes between non\u2010circulating B cells and circulating B cells, which illustrated their heterogeneity. Furthermore, we found high expression of CXCR3 on non\u2010circulating B cells, and the chemokine CXCL11 was also up\u2010regulated in the respiratory tissues, suggesting that CXCR3\u2010CXCL11 axis might accelerate the local resident of non\u2010circulating B cells in respiratory tract. Interestingly, intranasal immunization with BCG in mice elicited a sustained humoral immune response via induction of IgA and IgG Abs, which revealed the role of B cells. Meanwhile, tissue\u2010resident B cells, IgA<jats:sup>+<\/jats:sup> and IgG<jats:sup>+<\/jats:sup> memory B cells (MBCs) in respiratory tissues, as well as plasma cells in bone marrow, were expanded and maintained, and these subsets probably developed into antibody\u2010producing cells to participate in the local humoral immunity. Our data illustrate the phenotype and function of tissue B cells in the upper and lower airways, provide references for the prospective development of vaccines.<\/jats:p>","DOI":"10.1111\/jcmm.16278","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T04:12:20Z","timestamp":1611375140000},"page":"2621-2632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The phenotypic and functional study of tissue B cells in respiratory system provided important information for diseases and development of vaccines"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-2924","authenticated-orcid":false,"given":"Li","family":"Fan","sequence":"first","affiliation":[{"name":"Institute of Immunology Zhongshan School of Medicine Sun Yat\u2010sen University Guangzhou China"},{"name":"Medical College Hubei University of Arts and Science Xiangyang 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