Journal
AIDS
Volume 32, Issue 12, Pages 1571-1578Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001855
Keywords
B cell; innate immunity; macaques; natural killer cell; simian immunodeficiency virus
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Funding
- National Institutes of Health [P01 AI120756, R01 DE026014, R01 DE026327, R01 AI20828]
- Harvard Center for AIDS Research [P30 AI060354]
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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 identifyNKB cells in primates and study the impact of HIV/SIV-infections. Design and Methods: NKB cells were quantified in both naive 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, 0.01-0.2% 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 immunoglobulin 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 humans. Conclusion: These results suggest a cell type expressing both natural killer 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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