Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy

Scientific Reports
Lesley De ArmasSavita Pahwa

Abstract

Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. We used a fluorescent probe to isolate influenza H1N1-specific B cells and a multiplexed and targeted RT-PCR approach to measure expression levels of 96 genes involved in B cell activation and function. Gene profiling revealed a 4-gene predictive signature containing the phosphoinositide-3 kinase (PI3K) inhibitor, PTEN, for identifying antigen-specific MBC from HIV-infected individuals compared to healthy controls. Gene co-expression analysis showed that in addition to overexpression of PTEN, there was increased co-expression of type I interferon-associated genes wi...Continue Reading

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Citations

Oct 19, 2019·Clinical and Experimental Immunology·D AmodioP Palma
Mar 21, 2020·Frontiers in Microbiology·Gérémy SannierDaniel E Kaufmann
Jun 9, 2020·Journal of Immunology Research·Annalisa DalziniAnita De Rossi
Sep 11, 2019·Cold Spring Harbor Perspectives in Medicine·Henry TaylorHolm H Uhlig
May 20, 2021·Lab on a Chip·Roozbeh Abedini-Nassab, Sajjad Bahrami
Aug 23, 2021·Immunity & Ageing : I & a·Daniela FrascaSavita Pahwa

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Methods Mentioned

BETA
flow cytometry
RNA-Seq
Assay

Software Mentioned

DA
Azure Studio
R package “ mixOmics ”
TreeStar
Immunospot
PLSDA
FlowJo
PLS
MAST
R package “ glmnet ”

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