Regulation of subunit-specific germinal center B cell responses to the HIV-1 envelope glycoproteins by antibody-mediated feedback

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)