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 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.
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 naive and lentivirus infectedrhesus 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-infectedhumans. 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.
Authors: Michael Z Zulu; Kewreshini K Naidoo; Zenele Mncube; Manjeetha Jaggernath; Philip J R Goulder; Thumbi Ndung'u; Marcus Altfeld; Christina F Thobakgale Journal: AIDS Res Hum Retroviruses Date: 2017-09-21 Impact factor: 2.205
Authors: Mirzokhid Rakhmanov; Baerbel Keller; Sylvia Gutenberger; Christian Foerster; Manfred Hoenig; Gertjan Driessen; Mirjam van der Burg; Jacques J van Dongen; Elisabeth Wiech; Marcella Visentini; Isabella Quinti; Antje Prasse; Nadine Voelxen; Ulrich Salzer; Sigune Goldacker; Paul Fisch; Hermann Eibel; Klaus Schwarz; Hans-Hartmut Peter; Klaus Warnatz Journal: Proc Natl Acad Sci U S A Date: 2009-07-29 Impact factor: 11.205
Authors: James B Whitney; Alison L Hill; Srisowmya Sanisetty; Pablo Penaloza-MacMaster; Jinyan Liu; Mayuri Shetty; Lily Parenteau; Crystal Cabral; Jennifer Shields; Stephen Blackmore; Jeffrey Y Smith; Amanda L Brinkman; Lauren E Peter; Sheeba I Mathew; Kaitlin M Smith; Erica N Borducchi; Daniel I S Rosenbloom; Mark G Lewis; Jillian Hattersley; Bei Li; Joseph Hesselgesser; Romas Geleziunas; Merlin L Robb; Jerome H Kim; Nelson L Michael; Dan H Barouch Journal: Nature Date: 2014-07-20 Impact factor: 49.962
Authors: Iva Filipovic; Laura Chiossone; Paola Vacca; Russell S Hamilton; Tiziano Ingegnere; Jean-Marc Doisne; Delia A Hawkes; Maria Cristina Mingari; Andrew M Sharkey; Lorenzo Moretta; Francesco Colucci Journal: Nat Commun Date: 2018-10-29 Impact factor: 14.919