title: Disturbed homeostasis and multiple signaling defects in the peripheral blood B-cell compartment of patients with severe chronic sarcoidosis.
abstract: The presence of hypergammaglobulinemia, autoantibodies, and circulating immune complexes suggests that humoral immunity may contribute to the pathogenesis of sarcoidosis. However, little is known about the role played by B cells in the development of this disease. Here we investigated the subpopulation distribution, response to stimulation, and levels of the nuclear transcription factor NF-κB/p65 in peripheral blood B cells from patients with severe chronic sarcoidosis. Patients with severe chronic sarcoidosis had absolute B-cell lymphopenia and exhibited significantly decreased frequencies and total numbers of memory (CD19(+) CD27(+)) B cells. The reduced numbers of memory B cells in these patients reflected a decrease in the total numbers of class-switched (CD19(+) CD27(+) IgD(-)) and unswitched (CD19(+) CD27(+) IgD(+)) memory B cells and coincided with an increased frequency of circulating (CD19(+/-) CD20(-) CD27(++)) plasmablasts. Polyclonal stimulation of sarcoid B cells resulted in reduced expression of activation markers (i.e., CD25, CD69, and CD86), decreased proliferation, and impaired plasma cell differentiation. Baseline expression of p65 in B cells was reduced in 65% of the patients. These results suggest disturbed homeostasis, intrinsic signaling defects, and anergy within the peripheral B-cell compartments of patients with severe chronic sarcoidosis.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
authors.forename: Nam-Sihk
authors.initials: NS
authors.lastname: Lee
authors.forename: Laura
authors.initials: L
authors.lastname: Barber
authors.forename: Shaw M
authors.initials: SM
authors.lastname: Akula
authors.forename: George
authors.initials: G
authors.lastname: Sigounas
authors.forename: Yash P
authors.initials: YP
authors.lastname: Kataria
authors.forename: Sergio
authors.initials: S
authors.lastname: Arce
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000502:physiology*; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007072:Immunoglobulin D / Q000032:analysis; D007156:Immunologic Memory; D016131:Lymphocyte Subsets / Q000276:immunology*; D008231:Lymphopenia / Q000175:diagnosis; D008297:Male; D012507:Sarcoidosis / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D051996:Transcription Factor RelA / Q000032:analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D018941:Antigens, CD19; D007072:Immunoglobulin D; D051996:Transcription Factor RelA; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7