Show simple item record

Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

dc.contributor.author Nose, Brent
dc.contributor.author Arjunaraja, Swadhinya
dc.contributor.author Nosé, Brent D
dc.contributor.author Sukumar, Gauthaman
dc.contributor.author Lott, Nathaniel M
dc.contributor.author Dalgard, Clifton L
dc.contributor.author Snow, Andrew L
dc.date.accessioned 2019-08-09T19:15:37Z
dc.date.available 2019-08-09T19:15:37Z
dc.date.issued 2017
dc.identifier.issn 1664-3224
dc.identifier.issn 1664-3224
dc.identifier.uri https://hdl.handle.net/10161/19180
dc.description.abstract BENTA (B cell Expansion with NF-κB and T cell Anergy) disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-κB signaling. Despite dramatic polyclonal expansion of naïve and immature B cells, BENTA patients also present with signs of primary immunodeficiency, including markedly reduced percentages of class-switched/memory B cells and poor humoral responses to certain vaccines. Using purified naïve B cells from our BENTA patient cohort, here we show that BENTA B cells exhibit intrinsic defects in B cell differentiation. Despite a profound in vitro survival advantage relative to normal donor B cells, BENTA patient B cells were severely impaired in their ability to differentiate into short-lived IgDloCD38hi plasmablasts or CD138+ long-lived plasma cells in response to various stimuli. These defects corresponded with diminished IgG antibody production and correlated with poor induction of specific genes required for plasma cell commitment. These findings provide important mechanistic clues that help explain both B cell lymphocytosis and humoral immunodeficiency in BENTA disease.
dc.publisher Frontiers Media SA
dc.relation.ispartof Frontiers in Immunology
dc.relation.isversionof 10.3389/fimmu.2017.00913
dc.title Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells
dc.type Journal article
duke.contributor.id Nose, Brent|0902880
dc.date.updated 2019-08-09T19:15:36Z
pubs.begin-page 913
pubs.end-page 913
pubs.organisational-group Staff
pubs.organisational-group Duke
pubs.organisational-group Surgery
pubs.organisational-group Clinical Science Departments
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 8


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record