Comment[ArrayExpressAccession] E-GEOD-49019 MAGE-TAB Version 1.1 Public Release Date 2013-10-17 Investigation Title HIV-1 gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression via an α4β7-dependent mechanism Comment[Submitted Name] HIV-1 gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression via an α4β7-dependent mechanism Experiment Description The anti-HIV humoral immune response following acute infection is delayed and ineffective. HIV envelope protein gp120 binds to and signals through α4β7 on T cells. We show that gp120 also binds and signals through α4β7 on B cells, resulting in an abortive proliferative response. In primary B cells, gp120 signaling through α4β7 resulted in increased expression of TGF-β1 and the B cell inhibitory receptor FcRL4. Co-culture of B cells with HIV-infected autologous CD4+ T cells also resulted in increased B cell FcRL4 expression. These findings indicate that, in addition to inducing chronic immune activation, viral proteins can contribute directly to HIV-associated B cell dysfunction, thus providing a mechanism whereby the virus subverts the early HIV-specific humoral immune response. Forty-two samples in two batches were run with different treatments and different time points. Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Lempicki Jelicic Nawaz Huang Zheng Yang Lempicki Pascuccio Van Ryk Schwing Hiatt Wei Roby Cimbro David Hwang Kehrl Arthos Cicala Fauci Person First Name Richard Katija Fatima Da Xin Jun Richard Massimiliano Don Catherine Joe Danlan Greg Raffaello Antonio II John James Claudia Anthony Person Mid Initials W Y H Person Email geo@ncbi.nlm.nih.gov Person Affiliation NCI-Frederick Person Address NCI-Frederick, 1050 Boyles Street / P.O. Box B, Frederick, MD, USA Person Roles submitter Protocol Name P-GSE49019-1 P-GSE49019-5 P-GSE49019-6 P-GSE49019-2 P-GSE49019-3 P-GSE49019-4 P-GSE49019-7 Protocol Description Gene expression profiles were analyzed using Partek Genomic Suite 6.6. ID_REF = VALUE = Normalized expression value in log2 scale cRNA was labelled according to the manufacturer's recommended standard protocol for the Affymetrix Human Gene 1.0 ST microarray. Labeled cRNA was hybridized to the Affymetrix Human Gene 1.0 ST microarray according to the manufacturer's recommended standard protocol. Isolated B cells were treated with gp120 proteins of different affinity or mock protein. The exposure time points included 30min, 3hrs and 6hrs. Freshly isolated PBMCs were obtained from healthy donors and separated by Ficoll-Hypaque. Purified CD4+ T cells or B cells were obtained by negative selection using magnetic beads (StemCell Technologies, Vancouver, Canada). Cultured CD4+ cells were activated with OKT3, IL2 (20IU/ml) and all-trans retinoic acid (RA, 10nM) unless otherwise specified. RA was obtained from Sigma (St. Louis, MO) and discarded 1 month after reconstitution. cDNA of each sample was generated with Ambion WT Expression Kit. Hybridized Affymetrix human gene microarrays were scanned according to the manufacturer's recommended standard protocol. Protocol Type normalization data transformation protocol labelling protocol hybridization protocol sample treatment protocol growth protocol nucleic acid extraction protocol array scanning protocol Experimental Factor Name TIME GP120 TREATMENT Experimental Factor Type time gp120 treatment Comment[SecondaryAccession] GSE49019 Comment[GEOReleaseDate] 2013-10-17 Comment[ArrayExpressSubmissionDate] 2013-07-18 Comment[GEOLastUpdateDate] 2013-10-17 Comment[AEExperimentType] transcription profiling by array SDRF File E-GEOD-49019.sdrf.txt