NK-B cell cross talk induces CXCR5 expression on natural killer cells

B cell follicles (BCFs) in lymph nodes (LNs) are generally exempt of CD8(+) T and NK cells. African green monkeys (AGMs), a natural host of simian immunodeficiency virus (SIV), display NK cell-mediated viral control in BCF. NK cell migration into BCF in chronically SIVagm-infected AGM is associated with CXCR5(+) NK cells. We aimed to identify the mechanism leading to CXCR5 expression on NK cells. We show that CXCR5(+) NK cells in LN were induced following SIVagm infection. CXCR5(+) NK cells accumulated preferentially in BCF with proliferating B cells. Autologous NK-B cell co-cultures in transwell chambers induced CXCR5(+) NK cells. Transcriptome analysis of CXCR5(+) NK cells revealed expression of bcl6 and IL6R. IL-6 induced CXCR5 on AGM and human NK cells. IL6 mRNA was detected in LN at higher levels during SIVagm than SIVmac infection and often produced by plasma cells. Our study reveals a mechanism of B cell-dependent NK cell regulation.