title: BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation.
abstract: The activation of Toll-like receptor 9 (TLR9) expressed within B cells is associated with enhanced humoral immunity. However the role of TLR9 in the stimulation of B-cell responses, and more specifically in shaping the outcome of B-cell differentiation, remains unclear. Here, we observed that immunization with the TLR9 agonist CpG linked to protein antigen gave rise to enhanced production of antigen-specific class-switched antibodies in vivo. Unlike dendritic cells, B cells are unable to acquire these conjugates by macropinocytosis and instead depend on uptake through a signaling-competent B-cell receptor (BCR), provided the overall BCR-antigen avidity exceeds a defined threshold. The resultant stimulation of intrinsic TLR9 leads to enhanced antigen-specific B-cell proliferation and differentiation to form extrafollicular plasma cells. Thus, the direct conjugation of antigen and CpG reveals a mechanism that may operate during the initiation of primary immune responses, and may prove useful as a strategy for the design of adjuvants suitable for vaccinations.
authors.affiliation: Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Eckl-Dorna
authors.forename: Facundo D
authors.initials: FD
authors.lastname: Batista
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D018899:CpG Islands; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D000941:Antigens; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051217:Toll-Like Receptor 9; D009113:Muramidase