The RP105/MD‐1 complex: molecular signaling mechanisms and pathophysiological implications

Radioprotective 105 kDa (CD180) is an unusual TLR that lacks an intracellular Toll‐IL‐1R signaling domain and exhibits unconventional homodimerization behavior. Differential expression and functions of radioprotective 105 kDa have been associated with immune‐mediated pathologies, including infection, chronic inflammation, and autoimmune disorders. Radioprotective 105 kDa activates macrophages and B cells independently of canonical TLR signaling. Current understanding of the functional consequences of radioprotective 105 kDa signaling in B cells, macrophages, and dendritic cells indicates overlapping, but also some apparent opposing, cell‐specific roles for radioprotective 105 kDa in shaping cellular functions. This review compares interactions of radioprotective 105 kDa with its coreceptors, CD19, TLR4, and TLR2; integrates recent, novel findings on radioprotective 105 kDa‐mediated molecular signaling mechanisms; and summarizes current understanding of its contributions to infectious, inflammatory, and autoimmune disease. Review of how molecular signaling events driven by RP105 (CD180) shape the function of B cells, macrophages, and DCs.