B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses

被引:231
作者
Xu, SL [1 ]
Lam, KP [1 ]
机构
[1] Inst Mol & Cell Biol, Singapore 117609, Singapore
关键词
D O I
10.1128/MCB.21.12.4067-4074.2001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
B cell maturation protein (BCMA) is a member of the tumor necrosis factor (TNF) receptor family and is expressed in B lymphocytes. BCMA binds two TNF family members, BAFF and APRIL, that stimulate cellular proliferation. RAFF in particular has been shown to influence B-cell survival and activation, and transgenic mice overexpressing BAFF have a lupus like autoimmune disorder. We have inactivated BCMA in the mouse germ line. BCMA(-/-) mice have normal B-cell development, and the life span of mutant B lymphocytes is comparable to that of wild-type B cells. The humoral immune responses of BCMA(-/-) mice to T-cell-independent antigens as well as high and low doses of T-cell-dependent antigens are also intact. In addition, mutant mice have normal splenic architecture, and germinal centers are formed during an ongoing immune response. These data suggest a functional redundancy of BCMA in B-cell physiology that is probably due to the presence of TACI, another TNF receptor family member that is expressed on B cells and that can also bind BAFF and APRIL.
引用
收藏
页码:4067 / 4074
页数:8
相关论文
共 37 条
[1]   BAFF mediates survival of peripheral immature B lymphocytes [J].
Batten, M ;
Groom, J ;
Cachero, TG ;
Qian, F ;
Schneider, P ;
Tschopp, J ;
Browning, JL ;
Mackay, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (10) :1453-1465
[2]   Co-stimulation in T cell responses [J].
Chambers, CA ;
Allison, JP .
CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (03) :396-404
[3]   Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response [J].
Do, RKG ;
Hatada, E ;
Lee, H ;
Tourigny, MR ;
Hilbert, D ;
Chen-Kiang, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :953-964
[4]   GENERATION OF LONG-LIVED B-CELLS IN GERM-FREE MICE [J].
FORSTER, I ;
MULLER, W ;
SCHITTEK, B ;
RAJEWSKY, K .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (07) :1779-1782
[5]   Development and maturation of secondary lymphoid tissues [J].
Fu, YX ;
Chaplin, DD .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :399-433
[6]   BCMAP - AN INTEGRAL MEMBRANE-PROTEIN IN THE GOLGI-APPARATUS OF HUMAN MATURE B-LYMPHOCYTES [J].
GRAS, MP ;
LAABI, Y ;
LINARESCRUZ, G ;
BLONDEL, MO ;
RIGAUT, JP ;
BROUET, JC ;
LECA, G ;
HAGUENAUERTSAPIS, R ;
TSAPIS, A .
INTERNATIONAL IMMUNOLOGY, 1995, 7 (07) :1093-1106
[7]   Tumor necrosis factor receptor family members in the immune system [J].
Gravestein, LA ;
Borst, J .
SEMINARS IN IMMUNOLOGY, 1998, 10 (06) :423-434
[8]   TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease [J].
Gross, JA ;
Johnston, J ;
Mudri, S ;
Enselman, R ;
Dillon, SR ;
Madden, K ;
Xu, WF ;
Parrish-Novak, J ;
Foster, D ;
Lofton-Day, C ;
Moore, M ;
Littau, A ;
Grossman, A ;
Haugen, H ;
Foley, K ;
Blumberg, H ;
Harrison, K ;
Kindsvogel, W ;
Clegg, CH .
NATURE, 2000, 404 (6781) :995-999
[9]   APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth [J].
Hahne, M ;
Kataoka, T ;
Schröter, M ;
Hofmann, K ;
Irmler, M ;
Bodmer, JL ;
Schneider, P ;
Bornard, T ;
Holler, N ;
French, LE ;
Sordat, B ;
Rimoldi, D ;
Tschopp, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (06) :1185-1190
[10]   TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-κB, Elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase [J].
Hatzoglou, A ;
Roussel, J ;
Bourgeade, MF ;
Rogier, E ;
Madry, C ;
Inoue, J ;
Devergne, O ;
Tsapis, A .
JOURNAL OF IMMUNOLOGY, 2000, 165 (03) :1322-1330