Macrophages direct location-dependent recall of B cell memory to vaccination by Rama Dhenni,1,2,12 Albigail K. Grootveld,1ndrew N. McCorkinolange Obeid,6 Bra nupriya Aggarwal,3 Leonard D. Goldstein. Mee Ling Munier,3, ISBN 101016/JCELL202504005 instant download

Macrophages direct location-dependent recall of B cell memory to vaccination by Rama Dhenni,1,2,12 Albigail K. Grootveld,1ndrew N. McCorkinolange Obeid,6 Bra nupriya Aggarwal,3 Leonard D. Goldstein. Mee Ling Munier,3, ISBN 101016/JCELL202504005 instant download

SUMMARYVaccines generate long-lived plasma cells and memory B cells (Bmems) that may re-enter secondarygerminal centers (GCs) to further mutate their B cell receptor upon boosting and re-exposure to antigen.We show in mouse models that lymph nodes draining the site of primary vaccination harbor a subset ofBmems that reside in the subcapsular niche, generate larger recall responses, and are more likely to re-enterGCs compared with circulating Bmems in non-draining lymph nodes. This location-dependent recall ofBmems into the GC in the draining lymph node was dependent on CD169+ subcapsular sinus macrophages(SSMs) in the subcapsular niche. In human participants, boosting of the BNT162b2 vaccine in the same armgenerated more rapid secretion of broadly neutralizing antibodies, GC participation, and clonal expansion ofSARS-CoV-2-specific B cells than boosting of the opposite arm. These data reveal an unappreciated role forprimed draining lymph node SSMs in Bmem cell fate determination.