Anatomic redistribution of natural killer cells within secondary lymphoid organs during virus infection (VIR1P.1138)

Abstract

Abstract Natural killer (NK) cells are innate lymphocytes that classically function to restrict microbial infection and tumor development. NK cells are also important regulators of adaptive immunity. Specifically, we found that NK cells inhibited antiviral humoral immunity by restricting the germinal center (GC) response via a perforin-dependent cytotoxic mechanism during the initial few days of lymphocytic choriomeningitis virus (LCMV) infection. We hypothesize that this NK cell suppression of antiviral B cells requires redistribution of activated NK cells to regions of secondary lymphoid tissues where T-B cell interactions shape the GC reaction. NK cells were predominately localized within the red pulp of the spleens of uninfected mice, but infection with LCMV triggered a redistribution of NK cells to the white pulp. At day 3 p.i, many NK cells were present in T cell rich areas, most notably at the T-B cell interface where follicular helper T cells (TFH) typically reside. In addition, a small population of NK cells penetrated deep into the B cell follicles. The redistribution of NK cells was transient, with most NK cells returning to the red pulp by day 6 p.i. We speculate that white pulp localization is stimulated by altered expression of chemokine receptors by NK cells, and that this proximity to the GC facilitates direct interactions between NK cells and TFH or GC B cells, thereby contributing to diminished GC responses in the presence of NK cells.