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Cellular and humoral immunity in\n                    <jats:italic>Ot-<\/jats:italic>\n                    infected patients is not long-lasting, waning as early as one-year post-infection; however, its underlying mechanisms remain unclear. To date, no studies have examined germinal center (GC) or B cell responses in\n                    <jats:italic>Ot<\/jats:italic>\n                    -infected humans or experimental animals. This study was aimed at evaluating humoral immune responses at acute stages of severe\n                    <jats:italic>Ot<\/jats:italic>\n                    infection and possible mechanisms underlying B cell dysfunction. Following inoculation with\n                    <jats:italic>Ot<\/jats:italic>\n                    Karp, a clinically dominant strain known to cause lethal infection in C57BL\/6 mice, we measured antigen-specific antibody titers, revealing IgG2c as the dominant isotype induced by infection. Splenic GC responses were evaluated by immunohistology, co-staining for B cells (B220), T cells (CD3), and GCs (GL-7). Organized GCs were evident at day 4 post-infection (D4), but they were nearly absent at D8, accompanied by scattered T cells throughout splenic tissues. Flow cytometry revealed comparable numbers of GC B cells and T follicular helper (Tfh) cells at D4 and D8, indicating that GC collapse was not due to excessive death of these cell subtypes at D8. B cell RNAseq analysis revealed significant differences in expression of genes associated with B cell adhesion and co-stimulation at D8 versus D4. The significant downregulation of\n                    <jats:italic>S1PR2<\/jats:italic>\n                    (a GC-specific adhesion gene) was most evident at D8, correlating with disrupted GC formation. Signaling pathway analysis uncovered downregulation of 71% of B cell activation genes at D8, suggesting attenuation of B cell activation during severe infection. This is the first study showing the disruption of B\/T cell microenvironment and dysregulation of B cell responses during\n                    <jats:italic>Ot<\/jats:italic>\n                    infection, which may help understand the transient immunity associated with scrub typhus.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0011090","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T13:37:41Z","timestamp":1683293861000},"page":"e0011090","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alterations in germinal center formation and B cell activation during severe Orientia tsutsugamushi infection in 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