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PMID: 11085747 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

BAFF mediates survival of peripheral immature B lymphocytes.

The Journal of experimental medicine ·Vol. 192 ·No. 10 ·2000-11-20 ·Pages 1453-66

Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, Browning JL, Mackay F

Abstract

B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.

MeSH Terms
Animals Autoimmunity B-Cell Activating Factor B-Lymphocyte Subsets/cytology,immunology Cell Differentiation Cell Survival Cells, Cultured Hematopoietic Stem Cells/cytology,immunology Membrane Proteins/metabolism Mice Models, Immunological Spleen/cytology,immunology Tumor Necrosis Factor-alpha/metabolism
Chemicals
B-Cell Activating Factor Membrane Proteins Tnfsf13b protein, mouse Tumor Necrosis Factor-alpha
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Batten M
Department of Arthritis and Inflammation, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Groom J
Cachero T G
Qian F
Schneider P
Tschopp J
Browning J L
Mackay F
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.192.10.1453
Published
2000-11-20
Pages
1453-66
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193190
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.192.10.1453 PMC Full Text View journal details
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