title: Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients.
abstract: Complement receptors (CRs) play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35) is a potent inhibitor of the B cell receptor- (BCR-) induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs). Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.
authors.affiliation: MTA-ELTE Immunology Research Group, Budapest, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary.
authors.forename: Mariann
authors.initials: M
authors.lastname: Kremlitzka
authors.affiliation: Department of Immunology, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Mácsik-Valent
authors.affiliation: Institute of Rheumatology and Physiotherapy, Frankel Leo u. 25-29, Budapest 1023, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Polgár
authors.affiliation: Institute of Rheumatology and Physiotherapy, Frankel Leo u. 25-29, Budapest 1023, Hungary.
authors.forename: Emese
authors.identifier: 0000-0002-5399-2379
authors.initials: E
authors.lastname: Kiss
authors.affiliation: Institute of Rheumatology and Physiotherapy, Frankel Leo u. 25-29, Budapest 1023, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Poór
authors.affiliation: MTA-ELTE Immunology Research Group, Budapest, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary; Department of Immunology, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary.
authors.forename: Anna
authors.identifier: 0000-0002-3622-6680
authors.initials: A
authors.lastname: Erdei
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology* / Q000378:metabolism*; D000072377:Syk Kinase / Q000378:metabolism
chemical_list: D001323:Autoantibodies; C509991:CR1 protein, human; D011947:Receptors, Antigen, B-Cell; D017463:Receptors, Complement 3b; C000606896:SYK protein, human; D000072377:Syk Kinase; D020928:Mitogen-Activated Protein Kinases