Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19.
The Fc receptor (FcγRIIb) inhibits B cell responses when coengaged with B cell receptor (BCR), and has become a target for new autoimmune disease therapeutics. For example, BCR and FcγRIIb coengagement via the Fc-engineered anti-CD19 XmAb5871 suppresses humoral immune responses. We now assess effects of XmAb5871 on other activation pathways, including the pathogen-associated molecular pattern receptor, TLR9. Since TLR9 signaling is implicated in autoimmune diseases, we asked if XmAb5871 could inhibit TLR9 costimulation. We show that XmAb5871 decreases ERK and AKT activation, cell proliferation, cytokine, and IgG production induced by BCR and/or TLR9 signals. XmAb5871 also inhibited differentiation of citrullinated peptide-specific plasma cells from rheumatoid arthritis patients. XmAb5871 may therefore have potential to suppress pathogenic B cells in autoimmune diseases.
Department of Immunology; Eötvös Loránd University; Budapest, Hungary.
Dániel
D
Szili
Department of Immunology; Eötvös Loránd University; Budapest, Hungary.
Marcell
M
Cserhalmi
Department of Immunology; Eötvös Loránd University; Budapest, Hungary.
Zsuzsanna
Z
Bankó
Department of Rheumatology; Polyclinic of the Hospitaller Brothers of St. John of God; Budapest, Hungary.
György
G
Nagy
David E
DE
Szymkowski
Gabriella
G
Sármay
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000276:immunology
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D016207:Cytokines; C499173:FCGR2B protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
B cell; Fc-engineered; TLR; antibody therapy; autoimmune; humanized antibody; rheumatoid arthritis; signaling