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PMID: 12865416 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

BAFF selectively enhances the survival of plasmablasts generated from human memory B cells.

The Journal of clinical investigation ·Vol. 112 ·No. 2 ·2003-07-00 ·Pages 286-97

Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG

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.

MeSH Terms
ADP-ribosyl Cyclase/biosynthesis ADP-ribosyl Cyclase 1 Antigens, CD/biosynthesis Apoptosis B-Cell Activating Factor B-Cell Activation Factor Receptor B-Cell Maturation Antigen B-Lymphocytes/immunology,metabolism CD40 Ligand/metabolism Cell Differentiation Cell Division Cell Line Cell Separation Cell Survival Flow Cytometry Humans Immunologic Memory Interleukin-10/biosynthesis Interleukin-2/biosynthesis Membrane Glycoproteins Membrane Proteins/metabolism,physiology Microscopy, Fluorescence Models, Biological Neuropeptides/physiology Nuclear Proteins/physiology Protein Binding Receptors, Tumor Necrosis Factor/metabolism Spleen/cytology Time Factors Tumor Necrosis Factor-alpha/metabolism,physiology
Chemicals
ANP32B protein, human Antigens, CD B-Cell Activating Factor B-Cell Activation Factor Receptor B-Cell Maturation Antigen Interleukin-2 Membrane Glycoproteins Membrane Proteins Neuropeptides Nuclear Proteins Receptors, Tumor Necrosis Factor TNFRSF13C protein, human TNFRSF17 protein, human TNFSF13B protein, human Tumor Necrosis Factor-alpha Interleukin-10 CD40 Ligand ADP-ribosyl Cyclase CD38 protein, human ADP-ribosyl Cyclase 1
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Avery Danielle T
Centenary Institute of Cancer Medicine and Cell Biology, Newton, Australia.
Kalled Susan L
Ellyard Julia I
Ambrose Christine
Bixler Sarah A
Thien Marilyn
Brink Robert
Mackay Fabienne
Hodgkin Philip D
Tangye Stuart G
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI18025
Published
2003-07-00
Pages
286-97
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC164292
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1172/JCI18025 PMC Full Text View journal details
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