Abstract
The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases has clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B and T cell mediated autoimmune diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 387-401 |
| Number of pages | 15 |
| Journal | Autoimmunity Reviews |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2007 |
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Keywords
- Autoantibody
- Autoimmune
- CDR3
- Somatic hypermutation
- Spectratyping
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
B cells in autoimmune diseases : Insights from analyses of immunoglobulin variable (Ig V) gene usage. / Foreman, Angela Lee; Van de Water, Judith A; Gougeon, Marie Lise; Gershwin, M. Eric.
In: Autoimmunity Reviews, Vol. 6, No. 6, 06.2007, p. 387-401.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - B cells in autoimmune diseases
T2 - Insights from analyses of immunoglobulin variable (Ig V) gene usage
AU - Foreman, Angela Lee
AU - Van de Water, Judith A
AU - Gougeon, Marie Lise
AU - Gershwin, M. Eric
PY - 2007/6
Y1 - 2007/6
N2 - The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases has clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B and T cell mediated autoimmune diseases.
AB - The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases has clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B and T cell mediated autoimmune diseases.
KW - Autoantibody
KW - Autoimmune
KW - CDR3
KW - Somatic hypermutation
KW - Spectratyping
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UR - http://www.scopus.com/inward/citedby.url?scp=34249699643&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2006.12.005
DO - 10.1016/j.autrev.2006.12.005
M3 - Article
C2 - 17537385
AN - SCOPUS:34249699643
VL - 6
SP - 387
EP - 401
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
SN - 1568-9972
IS - 6
ER -