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By integrating spatial transcriptomics and single\u2010cell RNA sequencing of colorectal cancer, we delineate a B\u2010cell trajectory enriched for endoplasmic reticulum protein processing, autophagy, NF\u2010\u03baB signaling, and N\u2010linked glycosylation, highlighting SSR4 as a progressively induced TRAP\u2010complex component. SSR4 is further upregulated in B cells from anti\u2010PD\u20101 responders. B\u2010cell\u2010specific\n                    <jats:italic>Ssr4<\/jats:italic>\n                    deletion leads to peripheral B\u2010cell loss, reduced antibody output, exacerbated colitis, and impaired mucosal immunity. Mechanistically, SSR4 interacts with DDOST to regulate BAFFR N\u2010glycosylation, thereby sustaining B\u2010cell activation and LT\u03b11\u03b22 expression via NF\u2010\u03baB signaling. In\n                    <jats:italic>Apc<\/jats:italic>\n                    <jats:sup>Min\/+<\/jats:sup>\n                    mice,\n                    <jats:italic>Ssr4<\/jats:italic>\n                    deficiency accelerates tumorigenesis, disrupts TLS maturation, lowers serum IgG1, and increases high\u2010mannose (HM) Ig. Conversely, SSR4 overexpression in CHO cells reduces high\u2010mannose glycans and enhances IgG1 ADCC and CDC. These findings identify SSR4 as a central regulator of B\u2010cell glycosylation and TLS\u2010dependent anti\u2010tumor immunity, offering translational implications for immunotherapy and antibody engineering.\n                  <\/jats:p>","DOI":"10.1002\/advs.75790","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:53:57Z","timestamp":1779288837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SSR4 Sustains Tertiary Lymphoid Structures by Regulation Quality Control of N\u2010linked Glycosylation During B\u2010cell Differentiation Into Plasmacyte in Colorectal Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Wei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathology Nanjing First Hospital Nanjing Medical University  Nanjing Jiangsu 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