BAFF selectively enhances the survival of plasmablasts generated from human memory B cells
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Avery, Danielle T.; Kalled, Susan L.; Ellyard, Julia I.; Ambrose, Christine; Bixler, Sarah A.; Thien, Marilyn; Brink, Robert; Mackay, Fabienne; Hodgkin, Philip D.; Tangye, Stuart G.
Description
The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors — transmembrane activator of and CAML interactor (TACI), B cell...[Show more]
dc.contributor.author | Avery, Danielle T. | |
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dc.contributor.author | Kalled, Susan L. | |
dc.contributor.author | Ellyard, Julia I. | |
dc.contributor.author | Ambrose, Christine | |
dc.contributor.author | Bixler, Sarah A. | |
dc.contributor.author | Thien, Marilyn | |
dc.contributor.author | Brink, Robert | |
dc.contributor.author | Mackay, Fabienne | |
dc.contributor.author | Hodgkin, Philip D. | |
dc.contributor.author | Tangye, Stuart G. | |
dc.date.accessioned | 2016-03-21T03:30:13Z | |
dc.date.available | 2016-03-21T03:30:13Z | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | http://hdl.handle.net/1885/100838 | |
dc.description.abstract | The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors — transmembrane activator of and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R). To elucidate the contribution of BAFF to the differentiation of B cells into ISCs, we tracked the fate of human memory B cells stimulated with BAFF or CD40L. BAFF and CD40L significantly increased the overall number of surviving B cells. This was achieved via distinct mechanisms. CD40L induced proliferation of nondifferentiated blasts, while BAFF prevented apoptosis of ISCs without enhancing proliferation. The altered responsiveness of activated memory B cells to CD40L and BAFF correlated with changes in surface phenotype such that expression of CD40 and BAFF-R were reduced on ISCs while BCMA was induced. These results suggest BAFF may enhance humoral immunity in vivo by promoting survival of ISCs via a BCMA-dependent mechanism. These findings have wide-ranging implications for the treatment of human immunodeficiencies as well as autoimmune diseases. | |
dc.description.sponsorship | This work was supported by the National Health and Medical Research Council of Australia. S.G. Tangye was supported by a U2000 Postdoctoral Fellowship awarded by the University of Sydney. P.D. Hodgkin is a Senior Research Fellow of the National Health and Medical Research Council of Australia. F. Mackay is a Wellcome Trust Senior Research Fellow. | |
dc.publisher | American Society for Clinical Investigation | |
dc.rights | http://www.sherpa.ac.uk/romeo/issn/0021-9738..."author can archive publisher's version/PDF. Authors personal websites, institutional repositories and funding-body repositories" from SHERPA/RoMEO site (as at 21/03/16). | |
dc.source | Journal of Clinical Investigation | |
dc.subject | Keywords: B cell maturation antigen; BAFF receptor; CD40 ligand; immunoglobulin; protein BAFF; receptor; transmembrane activator and CAML interactor; tumor necrosis factor; unclassified drug; adenosine diphosphate ribosyl cyclase; ANP32B protein, human; B cell acti | |
dc.title | BAFF selectively enhances the survival of plasmablasts generated from human memory B cells | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 112 | |
dc.date.issued | 2003 | |
local.identifier.absfor | 060802 | |
local.identifier.ariespublication | u4133361xPUB86 | |
local.type.status | Published Version | |
local.contributor.affiliation | Avery, Danielle T, Garvan Institute of Medical Research, Australia | |
local.contributor.affiliation | Kalled, Susan L, Biogen Idec Inc, United States of America | |
local.contributor.affiliation | Ellyard, Julia, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University | |
local.contributor.affiliation | Ambrose, Christine, Biogen Idec Inc, United States of America | |
local.contributor.affiliation | Bixler, Sarah A, Biogen Idec Inc., United States of America | |
local.contributor.affiliation | Thien, Marilyn, Garvan Institute of Medical Research, Australia | |
local.contributor.affiliation | Brink, Robert, Garvan Institute of Medical Research, Australia | |
local.contributor.affiliation | Mackay, Fabienne, Garvan Institute of Medical Research, Australia | |
local.contributor.affiliation | Hodgkin, Phillip D, University of Sydney, Australia | |
local.contributor.affiliation | Tangye, Stuart, Garvan Institute of Medical Research, Australia | |
local.bibliographicCitation.issue | 2 | |
local.bibliographicCitation.startpage | 286 | |
local.bibliographicCitation.lastpage | 297 | |
local.identifier.doi | 10.1172/JCI18025 | |
dc.date.updated | 2016-06-14T08:59:03Z | |
local.identifier.scopusID | 2-s2.0-0041742400 | |
dcterms.accessRights | Open Access | |
Collections | ANU Research Publications |
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01_Avery_BAFF_selectively_enhances_the_2003.pdf | Published Version | 1.15 MB | Adobe PDF |
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