BAFF mediates survival of peripheral immature B lymphocytes.
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.
Batten
M
M
Department of Arthritis and Inflammation, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Groom
J
J
Cachero
T G
TG
Qian
F
F
Schneider
P
P
Tschopp
J
J
Browning
J L
JL
Mackay
F
F
D000818:Animals; D015551:Autoimmunity; D053264:B-Cell Activating Factor; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018448:Models, Immunological; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha