BAFF Mediates Survival of Peripheral Immature B Lymphocytes

doi:10.1084/jem.192.10.1453

Published online 20 November 2000.

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© The Rockefeller University Press, 0022-1007/2000/11/1453/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 10, November 20, 2000 1453-1466

Original Article

BAFF Mediates Survival of Peripheral Immature B Lymphocytes

Marcel Batten^a, Joanna Groom^a, Teresa G. Cachero^b, Fang Qian^b, Pascal Schneider^c, Jurg Tschopp^c, Jeffrey L. Browning^b, and Fabienne Mackay^a
^a Department of Arthritis and Inflammation, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
^b Department of Immunology, Department of Inflammation, the Department of Cell Biology, and the Department of Protein Engineering, Biogen Incorporated, Cambridge, Massachusetts 02142
^c Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland

Correspondence to: Fabienne Mackay, The Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, New South Wales 2010, Australia. Tel:61-2-9295-8414 Fax:61-2-9295-8404

B cell maturation is a very selective process that requiresfinely tuned differentiation and survival signals. B cell activationfactor from the TNF family (BAFF) is a TNF family member thatbinds to B cells and potentiates B cell receptor (BCR)-mediatedproliferation. A role for BAFF in B cell survival was suggestedby the observation of reduced peripheral B cell numbers in micetreated with reagents blocking BAFF, and high Bcl-2 levels detectedin B cells from BAFF transgenic (Tg) mice. We tested in vitrothe survival effect of BAFF on lymphocytes derived from primaryand secondary lymphoid organs. BAFF induced survival of a subsetof splenic immature B cells, referred to as transitional type2 (T2) B cells. BAFF treatment allowed T2 B cells to surviveand differentiate into mature B cells in response to signalsthrough the BCR. The T2 and the marginal zone (MZ) B cell compartmentswere particularly enlarged in BAFF Tg mice. Immature transitionalB cells are targets for negative selection, a feature thoughtto promote self-tolerance. These findings support a model inwhich excessive BAFF-mediated survival of peripheral immatureB cells contributes to the emergence and maturation of autoreactiveB cells, skewed towards the MZ compartment. This work providesnew clues on mechanisms regulating B cell maturation and tolerance.

Key Words: B cell maturation, autoimmunity, transitional B lymphocyte,spleen, antigen receptor

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