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 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.
Hondowicz
Brian D
BD
The Wistar Institute, Room 276, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Alexander
Shawn T
ST
Quinn
William J
WJ
Pagán
Antonio J
AJ
Metzgar
Michele H
MH
Cancro
Michael P
MP
Erikson
Jan
J
D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000637:transplantation; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism
D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C120197:BLyS receptor; C513179:CXCR5 protein, mouse; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; C486361:Tnfrsf13b protein, mouse; C490176:Tnfrsf17 protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein