title: Characterization of resident B cells of vascular walls in human atherosclerotic patients.
abstract: Animal models of atherosclerosis suggest that B cells have contradictory protective or proatherogenic effects that are also subset and context dependent. To further understand the pathophysiology of human atheroma, we characterized local Ig production and functional properties of resident B cells in human arterial lesions. Ig repertoires were analyzed by RT-PCR in carotid endarterectomy samples. Cytokine, differentiation marker and transcription factor mRNA expression was studied on arterial wall lymphocytes isolated by laser capture microdissection. Ig sequence analysis revealed that individual samples each contained a limited number of B cell clones. Functional α and γ mRNAs made up the majority of H chain mRNAs in the adventitia. Clonal evolution of Ig V regions, expression of activation-induced cytidine deaminase, clonal H chain switch, and an inverted λ/κ ratio of Ig L chain usage indicated that a local differentiation process was taking place in arterial walls. Clonotypic markers revealed different plaque and adventitia Ig repertoires and a B cell recirculation between adventitia and draining lymph nodes. Microdissected mononuclear cells had an activated phenotype expressing IL-6, GM-CSF, and TNF-α, whereas IL-2, IL-4, IL-10, M-CSF, and IFN-γ were not detected. Adventitial oligoclonal resident B cells of atherosclerotic patients are mainly mature B2 (conventional) CD20⁻ plasmablasts lacking markers of terminal differentiation to plasma cell (CD138 and Blimp-1). They present hallmarks of Ag-driven maturation and could act on inflammation and disease progression directly or by promoting polarization of other immune cells.
authors: Centre de Pharmacologie & Innovation dans le Diabète FRE 3400 Centre National de la Recherche Scientifique-Université Montpellier 1, 34093 Montpellier, France.
authors: Moustafa
authors: M
authors: Hamze
authors: Caroline
authors: C
authors: Desmetz
authors: Marie Laurence
authors: ML
authors: Berthe
authors: Pascal
authors: P
authors: Roger
authors: Nathalie
authors: N
authors: Boulle
authors: Pascal
authors: P
authors: Brancherau
authors: Eric
authors: E
authors: Picard
authors: Caroline
authors: C
authors: Guzman
authors: Claire
authors: C
authors: Tolza
authors: Paul
authors: P
authors: Guglielmi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002339:Carotid Arteries / Q000166:cytology / Q000276:immunology*; D002340:Carotid Artery Diseases / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction