Activation of B cells to produce antibodies is of central importance in defense against infectious agents. B cell activation is initiated by antigen recognition through the B cell antigen receptor (BCR) and requires additional activating signals such as those coming from helper T cells and/or other immune cells stimulated via innate recognition. Toll-like receptors (TLR) ligands may act on multiple cell types after immunization. Although it is clear that TLR signaling can promote antibody responses, there is little understanding of the rules governing how MyD88 and TLR signaling contribute to antibody responses in vivo.

In a recently study, Baidong Hou et al assessed the contribution of TLR signaling to T cell-dependent (TD) antibody responses by using mice lacking MyD88, a key signaling adaptor for most TLRs, in individual cell types. They demonstrated that, depending on the physical context in which a TLR ligand is presented, MyD88 signaling in either B cells or in DCs can substantially augment antibody responses to protein antigens combined with TLR ligands. In particular, DC but not B cell TLRs enhanced the antibody response to soluble protein antigens mixed with or chemically linked to a TLR ligand. In contrast, B cell MyD88 greatly enhanced the TD antibody response to a virus-like particle antigen that incorporated TLR ligands or to chemically inactivated influenza virus. Moreover, a dense array of antigenic epitopes on the viral particle promoted the ability of TLR signaling in the B cell to enhance the germinal center response. These results suggest that B cells are hard wired to respond vigorously to particles with the properties of many viruses and that this may represent an evolutionary adaptation that contributes to immune defense against virus infection. These insights may be useful in the development of more effective vaccines.

This work was published as an original article titled “Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center Response” on Immunity (Volume 34, Issue 3, 25 March 2011, Pages 375-384).