A number of microorganisms are capable of binding immunoglobulins (Igs) in a manner, which excludes binding to conventional antigen binding sites. Interaction of such bacterial proteins with surface immunoglobulins leads to polyclonal activation of B-lymphocytes. A recent example is Moraxella catarrhalis that binds to B lymphocytes in an IgD-dependent manner and induces proliferation and differentiation of B lymphocytes leading to the production of unspecific Igs. The activation is mediated by Moraxella IgD binding protein (MID), which specifically binds to both soluble IgD and the IgD B cell receptor (BCR). Besides cross-linking the BCR, whole Moraxella and outer membrane vesicles (OMVs) engage Toll like receptors (TLRs) to further increase the response. TLR activation leads to initiation of signaling pathways, which evoke a proinflammatory response against the invading microbes. Polyclonal B cell activation has in general been implicated in various phenomenons that are detrimental for the host but beneficial for pathogens, for example, autoimmune manifestations and redirection of the immune system.