title: Anti-Lipid IgG Antibodies Are ProducedviaGerminal Centers in a Murine Model Resembling Human Lupus.
abstract: Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigatein vivothe cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1-, CD19-, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD-, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identifiedin situthe presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute, Mexico City, Mexico; Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), IPN, Ciudad de México, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Wong-Baeza
authors.affiliation: Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), IPN , Ciudad de México , México.
authors.forename: Albany
authors.initials: A
authors.lastname: Reséndiz-Mora
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute , Mexico City , Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Donis-Maturano
authors.affiliation: Laboratorio de Inmunología Molecular II, Departamento de Inmunología, ENCB, IPN , Ciudad de México , México.
authors.forename: Isabel
authors.initials: I
authors.lastname: Wong-Baeza
authors.affiliation: Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), IPN , Ciudad de México , México.
authors.forename: Luz
authors.initials: L
authors.lastname: Zárate-Neira
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute , Mexico City , Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Yam-Puc
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute , Mexico City , Mexico.
authors.forename: Juana
authors.initials: J
authors.lastname: Calderón-Amador
authors.affiliation: Laboratory of monoclonal antibodies, Institute of Epidemiological Diagnosis and Reference , Mexico City , Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Medina
authors.affiliation: Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), IPN , Ciudad de México , México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Wong
authors.affiliation: Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), IPN , Ciudad de México , México.
authors.forename: Isabel
authors.initials: I
authors.lastname: Baeza
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute , Mexico City , Mexico.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Flores-Romo
keywords: anti-lipid IgG antibodies; antigen-specific cells; autoimmune disease; non-bilayer phospholipid arrangements; systemic lupus erythematosus