title: B cells from African American lupus patients exhibit an activated phenotype.
abstract: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19+CD27-IgD-double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies.
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Menard
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Sium
authors.initials: S
authors.lastname: Habte
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Gonsiorek
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lee
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Banas
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Holloway
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Nataly
authors.initials: N
authors.lastname: Manjarrez-Orduno
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Cunningham
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Stetsko
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Casano
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Selena
authors.initials: S
authors.lastname: Kansal
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Davis
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Carman
authors.affiliation: Immunoscience Translational Bioinformatics, Bristol-Myers Squibb Company, Pennington, New Jersey, USA.
authors.forename: Clarence K
authors.initials: CK
authors.lastname: Zhang
authors.affiliation: Division of Rheumatology, Northwell Health, Great Neck, New York, USA.
authors.forename: Ferva
authors.initials: F
authors.lastname: Abidi
authors.affiliation: Division of Rheumatology, Northwell Health, Great Neck, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Furie
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Nadler
authors.affiliation: Discovery Translational Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Suchard
mesh_terms: D001741:Black or African American; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology*; D051940:B7-2 Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D023201:CD40 Ligand / Q000032:analysis; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology*; D010641:Phenotype
chemical_list: D000954:Antigens, Surface; D051940:B7-2 Antigen; D019013:CD40 Antigens; D023201:CD40 Ligand