Baff Mediates Survival of Peripheral Immature B Lymphocytes

By M. Batten, J. Groom, T. Cachero, Fang Qian, P. Schneider, J. Tschopp, J. Browning, F. Mackay. Journal of Experimental Medicine, 2000

799 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/e759876e6a9ab6314ed0b42592af88a53014875e

How researchers see this paper

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In Immunology

1. S. Ghosh
2. M. Hayden
3. A. West
4. F. Mackay
5. J. Tschopp
6. C. Mackay
7. Shizuo Akira
8. N. Perkins

Citations in the corpus

• Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. (2002, background): “Excessive survival signals led to the massive expansion of the T2 B cell subset, but also the MZ B cell subset in BAFF Tg mice (20), supporting the possibility”
• PI3 Kinase signals BCR dependent mature B cell survival (2009, neutral): “In BAFF or BAFF-R deficient mice, mature B cells scarcely develop, and BAFF depletion in adult animals leads to rapid apoptosis of these cells (Batten et al., 2000; Thompson et al., 2000; Yan et al., 2001).”
• BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells (2002, result): “In contrast to our results, it is suggested that BAFF contributes to the survival of T2 and mature, but not purified, T1 B cell”
• The follicular versus marginal zone B lymphocyte cell fate decision (2009, background): “BAFF is also required for marginal zone B cell development, a requirement that seems to be separate from its role in promoting the survival of B cells in the follicl”
• NF-κB1 p50 Is Required for BLyS Attenuation of Apoptosis but Dispensable for Processing of NF-κB2 p100 to p52 in Quiescent Mature B Cells1 (2003, background): “In agreement, BLyS was subsequently found to enhance the survival of immature transitional type 2 (T2) B cells and marginal zone B cells in vitro (10).”
• BAFF: A fundamental survival factor for B cells (2002, background): “BAFF was found to specifically support the survival of T2 B cells in vitro”
• Decision making in the immune system: Regulation of B-cell fate by antigen-receptor signals (2002, neutral): “cgi?l=10673">BAFF ) is also crucial for this transitio”
• NF-κB and the immune response (2006, background): “Although both canonical and noncanonical NF-kB pathways are functional during B-cell development, recent work (Batten et al., 2000; Schiemann et al., 2001; Claudio et al., 2002) has underscored the importance of BAFF ligation in selectively activating the non-canonical NF-kB pathway and the…”