Bacterial CpG induces hyper-IgM production in CD27(+) memory B cells in primary biliary cirrhosis.
BACKGROUND AND AIMS: Sera from patients with primary biliary cirrhosis ( PBC) are characterized by the presence of antimitochondrial antibodies and elevated levels of immunoglobulin (Ig) M. We hypothesized that the increase in serum IgM is the result of chronic B-cell activation induced via the Toll-like receptor (TLR) signaling pathway. METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from patients with PBC and controls following incubation with CpG, a natural ligand for TLR9, and determined the basal and stimulated levels of intracellular IgM, the density of TLR9, and the contribution of specific B-cell subpopulations. RESULTS: Our data demonstrate uniquely that in vitro incubation of PBMCs from PBC with CpG-B, but not CpG-A, led to a markedly high frequency of intracellular IgM-positive B cells, associated with high levels of synthesized IgM and identified to be a function of CD27(+) memory B cells. This memory B-cell subset also expressed higher densities of TLR9 as compared with naive B cells. These results were not due to increased proliferation, as defined by 5-carboxyfluoresein diacetate succinimidyl ester labeling, or an increase in the life span of B cells, as defined by Bcl-2 expression. CONCLUSIONS: These findings for the first time identify a major role for innate immune mechanisms in the induction and persistence of abnormal humoral immune responses in PBC.[1]References
- Bacterial CpG induces hyper-IgM production in CD27(+) memory B cells in primary biliary cirrhosis. Kikuchi, K., Lian, Z.X., Yang, G.X., Ansari, A.A., Ikehara, S., Kaplan, M., Miyakawa, H., Coppel, R.L., Gershwin, M.E. Gastroenterology (2005) [Pubmed]
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