medRxiv PreprintsInternational11 November 2026
Dysregulated B Cell Education Drives Autoimmunity and Immunodeficiency in Down Syndrome
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Individuals with Down syndrome (DS) present with both increased rates of autoimmunity and immunodeficiency. To understand this paradox, we first examined lymph node (LN) architecture and immune cell composition in infants with and without DS, as well as peripheral blood B cells from unrelated adults with and without DS. Most strikingly, LNs from individuals with DS exhibited a marked paucity of germinal centers compared with typical lymph nodes. Stromal cells within DS LNs expressed significantly lower levels of the adhesion molecules ICAM1 and VCAM1, accompanied by significantly reduced CXCR5
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