title: Poke weed mitogen requires Toll-like receptor ligands for proliferative activity in human and murine B lymphocytes.
abstract: Poke weed mitogen (PWM), a lectin purified from Phytolacca americana is frequently used as a B cell-specific stimulus to trigger proliferation and immunoglobulin secretion. In the present study we investigated the mechanisms underlying the B cell stimulatory capacity of PWM. Strikingly, we observed that highly purified PWM preparations failed to induce B cell proliferation. By contrast, commercially available PWM preparations with B cell activity contained Toll-like receptor (TLR) ligands such as TLR2-active lipoproteins, lipopolysaccharide and DNA of bacterial origin. We show that these microbial substances contribute to the stimulatory activity of PWM. Additional experimental data highlight the capacity of PWM to enable B cell activation by immunostimulatory DNA. Based on these findings we propose that the lectin sensitizes B cells for TLR stimulation as described for B cell receptor ligation and that B cell mitogenicity of PWM preparations results from synergistic activity of the poke weed lectin and microbial TLR ligands present in the PWM preparations.
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany. isabelle.bekeredjian-ding@med.uni-heidelberg.de
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bekeredjian-Ding
authors.forename: Sandra
authors.initials: S
authors.lastname: Foermer
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Marijo
authors.initials: M
authors.lastname: Parcina
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051193:Toll-Like Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011043:Pokeweed Mitogens; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors