Antigen-induced B-cell death and elimination during germinal-centre immune responses.

Abstract:

:During an immune response, hypermutation of immunoglobulin genes in B cells proliferating within germinal centres (GCs) generates variant antibodies that react with higher affinity against either foreign or self antigens. Several experiments suggest that self-reactive B cells may be censored at this stage of the immune response, but the rarity of these cells and the dynamic nature of GC reactions have prevented direct analysis. We have developed a new approach to visualize the fate of antigen-specific B cells during GC reactions by seeding an ongoing immune response with lysozyme-specific B cells from immunoglobulin-gene transgenic animals. Administration of soluble antigen at the peak of the GC response rapidly eliminates lysozyme-specific GC B cells in two waves of apoptosis, one within the GC and a second in cells that have redistributed to lymphoid zones that are rich in T cells. Elimination of these cells is inhibited by constitutive expression of the follicular lymphoma proto-oncogene bcl-2. These findings reveal censoring steps that may normally prevent affinity maturation of autoantibodies to systemic autoantigens, and might be used by pathogenic microorganisms or in clinical strategies to interfere with antibody responses.

journal_name

Nature

journal_title

Nature

authors

Shokat KM,Goodnow CC

doi

10.1038/375334a0

subject

Has Abstract

pub_date

1995-05-25 00:00:00

pages

334-8

issue

6529

eissn

0028-0836

issn

1476-4687

journal_volume

375

pub_type

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