Human genetic variation reveals FCRL3 is a lymphocyte receptor for Yersinia pestis. Keener et al.

These data accompany the manuscript "Human genetic variation reveals FCRL3 is a lymphocyte receptor for Yersinia pestis." Yersinia pestis is the bacterium responsible for plague, one of the deadliest diseases in history. To discover human genetic determinants of Y. pestis infection, we utilized nearly a thousand genetically diverse lymphoblastoid cell lines in a cellular genome-wide association study. A nonsynonymous SNP, rs2282284 (N721S), in Fc receptor like 3 (FCRL3) was associated with bacterial invasion of host cells (p=9x10-8). Overexpressed FCRL3 facilitated attachment and invasion of Y. pestis and colocalized with Y. pestis at attachment sites. These properties were variably conserved across the FCRL family, revealing an Ig-like domain and signaling motifs shared by FCRL3 and FCRL5 to be necessary for attachment and invasion. Direct binding to FCRL5 extracellular domain was confirmed, and B cells (the primary cells that express FCRLs) were preferentially invaded by Y. pestis. Thus, Y. pestis hijacks FCRL proteins, possibly taking advantage of an immune receptor to create a lymphocyte niche during infection.
Summary statistics for the Hi-HOST GWAS of Y. pestis invasion were previously deposited at the Duke Data Repository (https://doi.org/10.7924/r43n2d008).