Scientific Publications by FDA Staff

Eur J Immunol 2007 Jul;37(7):1785-95

Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion.

Katsenelson N, Kanswal S, Puig M, Mostowski H, Verthelyi D, Akkoyunlu M

Akkoyunlu M (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Div Bacterial Parasit &Allergen Prod, 1410 Rockville Pike,HFM-428, Rockville, MD 20852 USA US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Div Bacterial Parasit &Allergen Prod, Rockville, MD 20852 USA US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Rockville, MD 20852 USA

The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.