Predominant Autoantibody Production by Early Human B Cell Precursors

@article{Wardemann2003PredominantAP,
  title={Predominant Autoantibody Production by Early Human B Cell Precursors},
  author={Hedda Wardemann and Sergey Yurasov and Anne Schaefer and James W. Young and Eric Meffre and Michel C. Nussenzweig},
  journal={Science},
  year={2003},
  volume={301},
  pages={1374 - 1377}
}
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities… Expand
B Cells Producing Pathogenic Autoantibodies
TLDR
This chapter summarizes the origin of autoantibodies and describes their pathogenicity in the context of some selected autoimmune diseases. Expand
B-cell tolerance checkpoints in health and autoimmunity.
The enormous diversity of the antibody repertoire is generated by two mechanisms: recombination of immunoglobulin (Ig) gene variable (V), diversity (D), and joining (J) gene segments during the earlyExpand
Regulation of B cell self-tolerance by BAFF.
  • R. Brink
  • Biology, Medicine
  • Seminars in immunology
  • 2006
TLDR
Elevated BAFF expression subverts B cell self-tolerance by rescuing self-reactive B cells normally deleted relatively late during maturation, which is resistant to rescue by BAFF. Expand
Regulation of B-cell development by antibody specificity.
TLDR
Evidence suggests that entry into a mature subset involves active B-cell receptor signaling and self-antigen-mediated positive selection. Expand
A checkpoint for autoreactivity in human IgM+ memory B cell development
TLDR
It is concluded that a third checkpoint selects against self-reactivity during IgM+ memory B cell development in humans and was implemented before the onset of somatic hypermutation. Expand
Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance.
TLDR
The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM, and this reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors. Expand
B-cell tolerance.
TLDR
How knowledge of checkpoints involving receptor editing, deletion, anergy and competition for growth factors may be used to gain a better understanding of transplant tolerance and the generation of alloantibodies is considered. Expand
Autoantibody selection and production in early human life.
TLDR
This issue of the JCI presents a molecular basis for the limited and common repertoire of antibodies produced by fetal B cells, which may be distinct from the abnormalities in B cell development described in patients with autoimmune diseases. Expand
B-cell self-tolerance in humans.
TLDR
Recent data on the self-reactive B-cell repertoire in healthy humans and in patients with autoimmunity is summarized. Expand
Antibodies: Eliminating the bad guys
  • E. Bell
  • Biology
  • Nature Reviews Immunology
  • 2003
TLDR
The extent of autoantibody production is established and indicates two stages at which self reactivity is modified, showing that self-reactive antibodies are eliminated at two distinct stages of development. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 33 REFERENCES
Receptor editing in self-reactive bone marrow B cells
TLDR
In mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Expand
Contribution of Receptor Editing to the Antibody Repertoire
TLDR
It is found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. Expand
Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus.
TLDR
The results indicate that immunoglobulins secreted by human monoclonal lymphoid cell lines can have polyspecific autoantibody functions, similar to those found in normal human polyclonal antibodies, in human monOClonal paraproteins and in natural monoklonal antibodies synthesized by murine or rat clones obtained from physiologically normal animals. Expand
Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice
TLDR
Findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance. Expand
Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes
TLDR
B-cell tolerance in transgenic mice using genes for IgM anti-H–2k MHC class I antibody is studied and it is suggested that very large numbers of autospecific B cells can be controlled by clonal deletion. Expand
B‐cell subsets and the mature ­preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”
TLDR
Findings indicate a functional heterogeneity within the mature B‐lymphocyte population, in contrast to FO B cells, that has the unique capacity to generate effector cells in early stages of the immune response against (particulate) antigens that are scavenged efficiently in these specialized anatomical sites. Expand
Receptor Editing Occurs Frequently during Normal B Cell Development
TLDR
It is suggested that receptor editing occurs at a surprisingly high frequency in normal B cells, as it is shown that RS recombination is frequently induced by, and inactivates, functionally rearranged κ loci. Expand
Atypical VH-D-JH rearrangements in newborn autoimmune MRL mice.
TLDR
B cells from the autoimmune-prone MRL mice have significantly increased numbers of atypical VH-D-JH rearrangements (D-D fusions and D inversions), which could confer an increased propensity to produce unusual VH and JH rearranged early in ontogeny. Expand
Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizion
TLDR
Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Expand
Immature surface Ig+ B cells can continue to rearrange kappa and lambda L chain gene loci
TLDR
It is shown that early during the differentiation of pre-B cells, upregulation of R AG-1 and RAG-2 expression go hand in hand with rearrangements of the Ig gene loci, and deposition of a complete Ig molecule on the surface of a B cell does not automatically stop the Ig-rearrangement machinery. Expand
...
1
2
3
4
...