title: Chondroitin sulfate activates B cells in vitro, expands CD138+ cells in vivo, and interferes with established humoral immune responses.
abstract: Glycosaminoglycans have anti-inflammatory properties and interact with a variety of soluble and membrane-bound molecules. Little is known about their effects on B cells and humoral immune responses. We show that CS but not dextran or other glycosaminoglycans induces a pronounced proliferation of B cells in vitro compared with TLR4 or TLR9 ligands. With the use of inhibitors and KO mice, we demonstrate that this proliferation is mediated by the tyrosine kinases BTK and Syk but independent of CD44. Antibodies against Ig-α or Ig-β completely block CS-induced B cell proliferation. Injection of CS in mice for 4-5 days expands B cells in the spleen and results in a marked increase of CD138(+) cells in the spleen that is dependent on BTK but independent of CD4(+) T cells. Long-term treatment with CS for 14 days also increases CD138(+) cells in the bone marrow. When mice were immunized with APC or collagen and treated with CS for up to 14 days during primary or after secondary immune responses, antigen-specific humoral immune responses and antigen-specific CD138(+) plasma cells in the bone marrow were reduced significantly. These data show that CD138(+) cells, induced by treatment with CS, migrate into the bone marrow and may displace other antigen-specific plasma cells. Overall, CS is able to interfere markedly with primary and fully established humoral immune responses in mice.
authors.affiliation: Departments of Internal Medicine I and.
authors.forename: Hilke
authors.initials: H
authors.lastname: Brühl
authors.affiliation: Institute for Animal Physiology, University of Munich, Munich, Germany; and.
authors.forename: Josef
authors.initials: J
authors.lastname: Cihak
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Nicole
authors.initials: N
authors.lastname: Goebel
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Talke
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Kerstin
authors.initials: K
authors.lastname: Renner
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Hermann
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Gomez
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Barbara
authors.initials: B
authors.lastname: Reich
authors.affiliation: Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jîŕi
authors.initials: J
authors.lastname: Plachý
authors.affiliation: Institute for Animal Physiology, University of Munich, Munich, Germany; and.
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangassinger
authors.affiliation: II, University Hospital Regensburg, Regensburg, Germany; matthias.mack@klinik.uni-regensburg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D000072377:Syk Kinase; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D002809:Chondroitin Sulfates; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000072377:Syk Kinase; C000606897:Syk protein, mouse
keywords: collagen-induced arthritis; glycosaminoglycans; plasma cells