Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract

Abstract

Objective Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in fact a subpopulation of B cells and exists in higher primates remains unclear. The objective of this study was to identify NKB cells in primates and study the impact of HIV/SIV infections. Design and Methods NKB cells were quantified in both naïve and lentivirus infected rhesus macaques and humans by excluding lineage markers (CD3, CD127), and positive Boolean gating for CD20, NKG2A/C and/or NKp46. Additional phenotypic measures were conducted by RNA-probe and traditional flow cytometry. Results Circulating cytotoxic NKB cells were found at similar frequencies in humans and rhesus macaques (range, 0.01 to 0.2% of total lymphocytes). NKB cells were notably enriched in spleen (median, 0.4% of lymphocytes), but were otherwise systemically distributed in tonsil, lymph nodes, colon, and jejunum. Expression of immunoglobulins was highly variable, but heavily favoured IgM and IgA rather than IgG. Interestingly, NKB cell frequencies expanded in PBMC and colon during SIV infection, as did IgG expression, but were generally unaltered in HIV-infected human subjects. Conclusion These results suggest a cell type expressing both NK and B cell features exists in rhesus macaques and humans and are perturbed by HIV/SIV infection. The full functional niche remains unknown, but the unique phenotype and systemic distribution could make NKB cells unique targets for immunotherapeutics or vaccine strategies.

Natural Killer-Like B Cells Secreting Interleukin-18 Induces a Proinflammatory Response in Periodontitis

“…The findings in the present study supported the existence of NKB cells as an independent cell population. Phenotypically, CD3 − CD19 + cells expressing NK cell-specific markers (NKp46 or NK1.1) were found in the blood and periodontium of both humans and mice, which was consistent with the previous report which showed that CD3 − CD20 + NKG2A + phenotyping was identified as NKB cells in rhesus macaques ( 25 ). Moreover, NKB cells were systemically found, but only expand in the gastrointestinal tract during simian immunodeficiency virus infected rhesus macaques.…”

“…Moreover, NKB cells were systemically found, but only expand in the gastrointestinal tract during simian immunodeficiency virus infected rhesus macaques. However, human immunodeficiency virus infection did not induce the expansion of peripheral NKB cells in humans ( 25 ). A more recent study by Ge et al ( 26 ) suggested that alcohol increased NKB cells' proportion and serum IL-18 expression in an experimental alcoholic liver injury murine model.…”

“…Moreover, elevated periodontal-infiltrating NKB cells positively correlated with the degree of periodontal supporting tissue destruction, revealing the possible contribution of NKB cells to periodontitis, although we could not detect periodontal-infiltrating NKB cells in patients after effective periodontal therapy. Collectively, we speculated that NKB cells were a distinct subpopulation to conventional B cells sharing several properties overlapping with NK cells ( 5 , 25 ), although the function of expanded NKB cells in periodontitis remained unclear.…”

Molecular definition of group 1 innate lymphoid cells in the mouse uterus

“…The role of these B-cell and myeloid markers on uterine ILC1s is unknown, and a recently described subset of NKB cells is controversial (S. Wang et al 2017; Kerdiles et al 2017), but might be induced in SIV and HIV infection (Manickam et al 2018). Phenotypic and functional heterogeneity of g1 ILCs has been reported across tissues (Sojka et al 2014; Robinette et al 2015).…”

Molecular definition of group 1 innate lymphoid cells in the mouse uterus

“…Genes associated with B-cells, or for protein turnover, antigen processing and presentation, as well as the macrophage-associated F4/80 marker are upregulated in ILC1s. The role of these B-cell and myeloid markers on uterine ILC1s is unknown, and a recently described subset of NKB cells is controversial 64 , 65 , but might be induced in SIV and HIV infection 66 . The deconvolution model we have applied here confirms that uterine g1 ILCs have expression profiles aligned with those of cell types other than NK cells and including myeloid cells.…”