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Regulation of subunit-specific germinal center B cell responses to the HIV-1 envelope glycoproteins by antibody-mediated feedback
KTH, School of Biotechnology (BIO), Gene Technology.
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2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, no JUN, article id 738Article in journal (Refereed) Published
Abstract [en]

The regulation of germinal center (GC) B cell responses to single epitopes is well investigated. How monoclonal B cells are regulated within the polyclonal B cell response to protein antigens is less so. Here, we investigate the primary GC B cell response after injection of mice with HIV-1 envelope glycoproteins. We demonstrate that single GCs are seeded by a diverse number of B cell clones shortly after a single immunization and that the presence of Env-specific antibodies can inhibit the development of early GC B cells. Importantly, the suppression was dependent on the GC B cells and the infused antibodies to target the same subunit of the injected HIV-1 envelope glycoproteins. An affinity-dependent antibody feedback has previously been shown to regulate GC B cell development. Here, we propose that this antibody-based feedback acts on GC B cells only if they target the same or overlapping epitopes. This study provides important basic information of GC B cell regulation, and for future vaccine designs with aim to elicit neutralizing antibodies against HIV-1.

Place, publisher, year, edition, pages
Frontiers Media S.A. , 2017. Vol. 8, no JUN, article id 738
Keywords [en]
Envelope glycoproteins, Epitope-specific antibodies, Epitope-specific B cells, HIV-1, Regulation of germinal centers, virus glycoprotein, affinity chromatography, animal tissue, antibody mediated rejection, Article, biotinylation, cell selection, cellular immunity, clonogenesis, controlled study, enzyme linked immunosorbent assay, feedback system, flow cytometry, genome size, germinal center, Human immunodeficiency virus 1, immunization, immunofluorescence microscopy, immunohistochemistry, laser microdissection, mouse, nonhuman, polymerase chain reaction
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Genetics
Identifiers
URN: urn:nbn:se:kth:diva-216319DOI: 10.3389/fimmu.2017.00738ISI: 000404584400001Scopus ID: 2-s2.0-85021752860OAI: oai:DiVA.org:kth-216319DiVA, id: diva2:1150942
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QC 20171020

Available from: 2017-10-20 Created: 2017-10-20 Last updated: 2017-11-29Bibliographically approved

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Kvastad, Linda

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