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PMID: 19421318 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Crucial role for BAFF-BAFF-R signaling in the survival and maintenance of mature B cells.

PloS one ·Vol. 4 ·No. 5 ·2009-00-00 ·Pages e5456

Rauch M, Tussiwand R, Bosco N, Rolink AG

Abstract

Defects in the expression of either BAFF (B cell activating factor) or BAFF-R impairs B cell development beyond the immature, transitional type-1 stage and thus, prevents the formation of follicular and marginal zone B cells, whereas B-1 B cells remain unaffected. The expression of BAFF-R on all mature B cells might suggest a role for BAFF-R signaling also for their in vivo maintenance. Here, we show that, 14 days following a single injection of an anti-BAFF-R mAb that prevents BAFF binding, both follicular and marginal zone B cell numbers are drastically reduced, whereas B-1 cells are not affected. Injection of control, isotype-matched but non-blocking anti-BAFF-R mAbs does not result in B cell depletion. We also show that this depletion is neither due to antibody-dependent cellular cytotoxicity nor to complement-mediated lysis. Moreover, prevention of BAFF binding leads to a decrease in the size of the B cell follicles, an impairment of a T cell dependent humoral immune response and a reduction in the formation of memory B cells. Collectively, these results establish a central role for BAFF-BAFF-R signaling in the in vivo survival and maintenance of both follicular and marginal zone B cell pools.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology B-Cell Activating Factor/metabolism B-Cell Activation Factor Receptor/metabolism B-Lymphocytes/cytology,metabolism Cell Differentiation Cell Survival/physiology Cells, Cultured Female Flow Cytometry Immunization Immunoenzyme Techniques Mice Mice, Inbred C57BL Mice, Transgenic Proto-Oncogene Proteins c-bcl-2/physiology Rats Rats, Inbred Lew Spleen/immunology,metabolism
Chemicals
Antibodies, Monoclonal B-Cell Activating Factor B-Cell Activation Factor Receptor Proto-Oncogene Proteins c-bcl-2 Tnfrsf13c protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rauch Melanie
Developmental and Molecular Immunology, Department of Biomedicine (DBM), University of Basel, Basel, Switzerland.
Tussiwand Roxane
Bosco Nabil
Rolink Antonius G
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0005456
Published
2009-00-00
Epub
2009-00-06
Pages
e5456
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2673681
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0005456 PMC Full Text View journal details
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