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Mustafa Akkoyunlu, Sunita Kanswal, Nora Katsenelson, Severely reduced B cell TACI expression in newborn mice lead to impaired BAFF or APRIL induced immunoglobulin secretion (95.13), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S179, https://doi.org/10.4049/jimmunol.178.Supp.95.13
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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.