Expression of Toll-like receptors (TLRs) in B cells provides a cell-intrinsic mechanism for innate signals regulating adaptive immune responses. In combination with other signaling pathways in B cells, including through the B-cell receptor (BCR), TLR signaling plays multiple roles in B-cell differentiation and activation. The outcome of TLR signaling in B cells is largely context-dependent, which partly explains discrepancies among in vitro and in vivo studies, or studies using different immunogens. We focus on recent findings on how B-cell-intrinsic TLR signaling regulates antibody responses, including germinal center formation and autoantibody production in autoimmune disease models. In addition, TLR signaling also acts on the precursors of B cells, which could influence the immune response of animals by shaping the composition of the immune system. With TLR signaling modulating immune responses at these different levels, much more needs to be understood before we can depict the complete functions of innate signaling in host defense.