The role of BLyS/BLyS receptors in anti-chromatin B cell regulation

B lymphocyte stimulator (BLyS), also known as B cell-activating factor, is a key positive regulator of B cell homeostasis, and elevated levels of BLyS have been observed in systemic lupus erythematosus (SLE) patients. Given that anti-chromatin auto-antibodies are one of the hallmarks of SLE, we exam...

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Bibliographic Details
Published in:International immunology 2007-04, Vol.19 (4), p.465-475
Main Authors: Hondowicz, Brian D., Alexander, Shawn T., Quinn, William J., Pagán, Antonio J., Metzgar, Michele H., Cancro, Michael P., Erikson, Jan
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Antibodies, Antinuclear - blood
Antibodies, Antinuclear - immunology
Antibody Formation - drug effects
Antibody Formation - immunology
auto-antibody
autoimmunity
B-Cell Activating Factor - pharmacology
B-Cell Activation Factor Receptor - genetics
B-Cell Activation Factor Receptor - metabolism
B-Cell Maturation Antigen - genetics
B-Cell Maturation Antigen - metabolism
B-Lymphocyte Subsets - drug effects
B-Lymphocyte Subsets - immunology
B-Lymphocyte Subsets - metabolism
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Cell Differentiation - drug effects
Cell Differentiation - immunology
cytokines
Female
Gene Expression
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - metabolism
Immunoglobulin Heavy Chains - genetics
Immunoglobulin kappa-Chains - genetics
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Receptors, Chemokine - genetics
Receptors, Chemokine - metabolism
Receptors, CXCR5
Receptors, Tumor Necrosis Factor - genetics
Receptors, Tumor Necrosis Factor - metabolism
Spleen - cytology
Spleen - drug effects
Spleen - immunology
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Helper-Inducer - transplantation
Transmembrane Activator and CAML Interactor Protein - genetics
Transmembrane Activator and CAML Interactor Protein - metabolism
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Summary:B lymphocyte stimulator (BLyS), also known as B cell-activating factor, is a key positive regulator of B cell homeostasis, and elevated levels of BLyS have been observed in systemic lupus erythematosus (SLE) patients. Given that anti-chromatin auto-antibodies are one of the hallmarks of SLE, we examined the role of BLyS and its receptors in the regulation of anti-chromatin B cells. We demonstrate that exogenous BLyS treatment leads to an increase in B cell numbers, particularly anti-chromatin B cells; yet, their localization in the spleen and auto-antibody production remain unaffected. We also examined transmembrane activator and CAML interactor (TACI), BLyS receptor 3 (BR3) and B cell maturation antigen expression on anti-chromatin B cells before and after receiving T cell help. Interestingly, in the absence of T cell help, TACI expression is greater on immature anti-chromatin B cells compared with immature Tg(−) B cells, whereas BR3 levels are comparable. After receiving T cell help, the anti-chromatin B cells that have differentiated into short-lived plasma cells no longer express BR3 but retain TACI. These data suggest a novel role for TACI in anti-chromatin B cell homeostasis and differentiation.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxm011