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

BD Hondowicz, ST Alexander… - International …, 2007 - academic.oup.com
BD Hondowicz, ST Alexander, WJ Quinn III, AJ Pagán, MH Metzgar, MP Cancro, J Erikson
International immunology, 2007academic.oup.com
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 …
Abstract
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.
Oxford University Press