Spleen tyrosine kinase-mediated B-cell receptor signaling is required for optimal induction of toll-like receptor 9 and TNF receptor-associated factor 6, according to new data that also conclude this process allows efficient propagation of toll-like receptor 9-mediated signaling in memory B cells.
Researchers used combinations of anti-B-cell receptor (BCR), soluble CD40 ligand and CpG to stimulate human naïve and memory B cells. They observed activation of BCR synergized with CD40 and TLR9-mediated signals, driving proliferation, cell-cycle progression, expression of costimulatory molecules, cytokine production and immunoglobulin production of human B-cell subsets, notably memory B cells.
The Syk inhibitor abrogated these B-cell functions, researchers noted, and after stimulation through all three receptors, B-cell subsets induced expression of TLR9, TRAF6 and phospho-nuclear factor kB, which was also significantly abrogated by the Syk inhibitors.
“Syk inhibitors might be promising for controlling the aberrant TLR9 signaling that is related to the proliferation and differentiation of pathogenic memory B cells in patients with autoimmune diseases, including [systemic lupus erythematosus] and [rheumatoid arthritis],” the researchers wrote.