| Summary |
Natural killer-like B (NKB) cells are unique innate immune cells that express both natural killer (NK) and B cell markers. They act as first responders by secreting IL-18 upon infection, thus inducing the critical cascade of innate and adaptive immune cell infiltration and activation. However, limited research exists on the role of NKB cells in homeostasis, and infection in primates. Therefore, we investigated the signaling and trafficking proteome, in situ localization and transcriptome of NKB cells in comparison to conventionally defined NK and B cells. Intracellular signaling proteins and trafficking markers were expressed differentially on naïve NKB characterized by high expression of CD62L and Syk, and low expression of CD69, a4b7, FcRg, Zap70, and CD3z which were more similar to B cells than NK cells. CD20+NKG2a/c+ NKB cells were identified in spleen, mesenteric lymph nodes (MLN), colon, jejunum, and liver of naïve RM by tissue imaging with NKB cell counts concentrated in spleen and MLN. Transcriptomic analysis of naïve splenic NKB cells by scRNAseq showed that NKB cells undergo somatic hypermutation and express Ig receptors, similar to B cells. While only 15% of sorted NKB population showed transcript expression of both KLRC1 (NKG2A) and MS4A1 (CD20), cells expressing KLRC1, MS4A1and IgH/IgL transcripts were only 5%. However, we observed expanded NKB frequencies in gut mucosa as early as 35 days and in buccal mucosa as early as 14 days post-SIV infection using an RM model of HIV infection, thus indicating NKB cells, though infrequent, could have potential roles to play in mucosal infections.
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