The Journal of Immunology, 2007, 178: 95.13.
Copyright © 2007 by The American Association of Immunologists, Inc.
Severely reduced B cell TACI expression in newborn mice lead to impaired BAFF or APRIL induced immunoglobulin secretion
Mustafa Akkoyunlu,
Sunita Kanswal and
Nora Katsenelson
Division of Bacterial Parasitic and Allergenic Products, FDA/CBER, 29 Lincoln Drive, Building 29, Room 406, Bethesda, MD, 20892
Abstract
In this study, we investigated the expression and the functions of the TNF family cytokines BAFF and APRIL, and their receptors (BAFF-R, BCMA and TACI) in newborn mice. We found that while macrophage BAFF and APRIL expressions were increased, B cell TACI expression was dramatically reduced (p<0.001) in newborns. Since TACI is shown to be important in BAFF/APRIL mediated IgA and IgG isotype switch and secretion, we analyzed the effect of BAFF and APRIL on newborn B cells and showed that both BAFF and APRIL failed to induce IgA or IgG secretion. We have previously shown that (manuscript in revision) the CpG-ODNs up-regulate the expression of TACI on adult mouse B cells and augment BAFF/APRIL mediated IgA/IgG secretion. We therefore studied the effect of CpG-ODNs on the expression of TACI and found that as with adult B cells, newborn mice also manifested increased TACI expression (p 
0.0001) after stimulation with CpG-ODN. Moreover, CpG-ODN pretreatment of B cells rendered them susceptible to BAFF or APRIL mediated IgA/IgG secretion. Similarly, in in vivo experiments, CpG injected newborn mice showed increased TACI expression and ex vivo stimulation of B cells from these mice with BAFF or APRIL yielded increased IgA/IgG secretion. Given the pivotal role of TACI in mediating antibody responses to polysaccharide vaccines, low TACI expression could be a possible contributing factor to the susceptibility of newborns to infections with encapsulated bacteria.
