title: CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection.
abstract: The immunomodulatory receptor CD300a is expressed on human B cells. Naive B cells express very low levels of this receptor, whereas memory B cells and plasmablasts/cells express variable levels of CD300a. Germinal center B cells are negative for CD300a expression. Stimulation of naive B cells via B-cell receptor (BCR) and Toll-like receptor 9, along with T-cell help, failed to up-regulate CD300a cell surface expression despite the increased expression of the memory marker CD27 and the down-regulation of CD305. However, Toll-like receptor 9 stimulation alone significantly increased CD300a expression on memory B cells, whereas interleukin-4 and transforming growth factor-β1 act as negative regulators of CD300a expression on memory B cells. Coligation of BCR and CD300a inhibits Ca(2+) mobilization and nuclear factor of activated T cell transcriptional activity evoked by BCR ligation alone. Suppression of CD300a expression in primary B cells with siRNA resulted in increased BCR-mediated proliferation, thereby confirming the inhibitory capacity of CD300a. Finally, we show that CD300a expression levels are significantly down-regulated in the circulating B cells of HIV-infected patients. Altogether, these data demonstrate a novel mechanism for suppressing the activity of B cells and suggest a potential role for CD300a in the B-cell dysfunction observed in HIV-induced immunodeficiency.
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Silva
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Lela
authors.initials: L
authors.lastname: Kardava
authors.forename: Karen
authors.initials: K
authors.lastname: Debell
authors.forename: Venkateswara R
authors.initials: VR
authors.lastname: Simhadri
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: José
authors.initials: J
authors.lastname: Peña
authors.forename: John E
authors.initials: JE
authors.lastname: Coligan
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrego
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D018450:Disease Progression; D015536:Down-Regulation; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008156:Luciferases / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; C515070:CD300A protein, human; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D008156:Luciferases