Therefore, CpG ODN and LPS are not synergy in B cell proliferation due to the synergistic induction of large amounts of IL-10. Consistent with these findings, we observed that bacterial genomic DNA also greatly enhanced LPStriggered IL-10 production, but to a lesser extent than CpG ODN. Bacterial DNA and LPS had neither additive nor synergetic effect on naı ¨ve B cell proliferation, although both stimulants were potent mitogens for B cells. In addition, the immunosuppressive effect of IL-10 on CpG ODN-stimulated Ig-secreting cell generation was also previously reported. Similarly, we found that stimulation with bacterial DNA along with LPS did not enhance differentiation into plasma cells. In contrast, stimulation with ALD-DNA alone had no effect on IL-10 expression and slightly increased Doxorubicin LPS-triggered IL-10 production. Taken together, the data indicate that ALD-DNA is functionally distinct from CpG ODN and bacterial genomic DNA, and is able to enhance LPS-mediated proliferation and plasma cell generation in part due to its weak ability to enhance LPS-triggered IL-10 production. Remarkably, we found that ALD-DNA treated lupus B cells were able to induce surface CD138 and secrete IgM. ALD-DNA slightly increased XBP1 and Blimp-1 mRNA expression. These data suggested that ALD-DNA at least partially activated plasma cell differentiation and promoted a subset of lupus B cells to become IgM-secreting plasmablasts/plasma cells. In contrast, ALD-DNA alone had little effect on the increases in CD138 cell numbers, antibody production and mRNA levels of XBP1 and Blimp-1 in normal naive B cells. Therefore, lupus B cells appear to be more sensitive to ALD-DNA stimulation than normal B cells. Furthermore, ALD-DNA enhanced LPS-triggered plasmablast/plasma cell differentiation program of lupus B cells, as evidenced by increases in CD138 + cell numbers, XBP1 and Blimp-1 mRNA expression as well as IgM production. The ELISA data indicated that ALD-DNA enhanced LPSinduced IgG, but not IgM, production in normal naı ¨ve B cells. In striking contrast, ALD-DNA promoted LPS-induced IgM, but not IgG, production in lupus B cells. Therefore, ALD-DNA had distinct effect on antibody production in normal and lupus B cells, at least under these in vitro culture conditions. IL-6 is a survival factor for plasma cells and acts as a nonswitching factor to enhance IgG production by committed B cells. ALD-DNA promoted LPS-induced IL-6 expression in normal naı ¨ve B cells and this finding may in part account for the increased IgG production. Conversely, ALD-DNA did not enhance LPS-induced IL-6 expression in lupus B cells. The mechanisms that enable ALD-DNA to selectively stimulate IgM production by lupus B cells, but not normal B cells, remain unclear. Moreover, lupus B cells showed higher responsiveness than normal B cells to ALD-DNA and/or LPS stimulation to undergo terminal differentiation and yielded higher antibody production. These differential effects might be partially attributable to the distinct B cell subset composition. Our result also confirmed this abnormality. MZ B cells are programmed for efficient differentiation into mature plasma cells with the ability to secrete massive quantities of IgM in response to TLR agonists such as LPS.