Anti-viral and anti-commensal antibody repertoires differ across human tissues 3554

Abstract Description Memory B cells (BRMs) are present in serum, lymphoid organs and non-lymphoid tissues, where they are strategically positioned to provide immediate protection at mucosal and barrier sites. We previously reported that in children aged 1–3 years, BRMs from the lung and lung-associated lymph nodes (LLNs) showed a strong bias toward respiratory pathogens, contrasting with vaccine-specific antibodies (Abs) in serum. To study BRM tissue localization in adults, we used samples from lung, LLN, mesenteric lymph node (MLN), spleen (SPL) bone marrow (BOM) and blood (BLD) from 23 adult donors. Cells were stimulated in-vitro to differentiate into Ab-secreting plasma cells. Using antigen microarrays covering antigens from childhood vaccines, human herpes viruses, common respiratory viruses, and commensal bacteria and fungi, we profiled secreted IgG and IgA and compared these to the serum Ab repertoires. We found significant differences in antigen-specific repertoires across tissues, with both tissue-specific and shared specificities. Responses to childhood vaccines and viruses were more tissue-specific, while responses to commensal bacteria and fungi were more widespread. High anti-CMV titers were associated with reduced anti-commensal responses to some bacterial families. Our findings provide insights into the interplay between tissue-specific immunity and systemic Ab responses, offering valuable information on immune surveillance and defense mechanisms across human tissues. Funding Sources ISF 2683/21 Topic Categories Mucosal and Regional Immunology (MUC)