Checkpoint receptors and their cognate ligands are frequently targeted in autoimmune disorders by B and T cells, wherein these adaptive immune responses are likely to significantly contribute to the underlying immunopathology. A novel technology for the clonal elimination of autoreactive B cells that targets checkpoint receptors and their ligands is described herein. One embodiment of this technology is a checkpoint receptor or ligand extracellular domain molecular chimera with an effector domain, which is capable of inducing B cell apoptosis, necrosis, and/or tolerization/anergization: herein, this technology is referred as Pantlds (polyclonal anti-idiotypics). In other embodiments, this technology also includes effector molecular chimeras with immunoregulatory cytokines. Novel apoptotic effectors are also described. Methods for the identification of checkpoint receptor/ligand autoreactive B cell responses, construction of Pantlds, and their in vitro and in vivo application are also described.
