B-cell-activating factor inhibits CD20-mediated and B-cell receptor-mediated apoptosis in human B cells.
B-cell-activating factor (BAFF) is a survival and maturation factor for B cells belonging to the tumour necrosis factor superfamily. Among three identified functional receptors, the BAFF receptor (BAFF-R) is thought to be responsible for the effect of BAFF on B cells though details of how remain unclear. We determined that a hairy-cell leukaemia line, MLMA, expressed a relatively high level of BAFF-R and was susceptible to apoptosis mediated by either CD20 or B-cell antigen receptor (BCR). Using MLMA cells as an in vitro model of mature B cells, we found that treatment with BAFF could inhibit apoptosis mediated by both CD20 and BCR. We also observed, using immunoblot analysis and microarray analysis, that BAFF treatment induced activation of nuclear factor-kappaB2 following elevation of the expression level of Bcl-2, which may be involved in the molecular mechanism of BAFF-mediated inhibition of apoptosis. Interestingly, BAFF treatment was also found to induce the expression of a series of genes, such as that for CD40, related to cell survival, suggesting the involvement of a multiple mechanism in the BAFF-mediated anti-apoptotic effect. MLMA cells should provide a model for investigating the molecular basis of the effect of BAFF on B cells in vitro and will help to elucidate how B cells survive in the immune system in which BAFF-mediated signalling is involved.
Department of Developmental Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Yohei
Y
Saito
Yoshitaka
Y
Miyagawa
Keiko
K
Onda
Hideki
H
Nakajima
Ban
B
Sato
Yasuomi
Y
Horiuchi
Hajime
H
Okita
Yohko U
YU
Katagiri
Masahiro
M
Saito
Toshiaki
T
Shimizu
Junichiro
J
Fujimoto
Nobutaka
N
Kiyokawa
D018951:Antigens, CD20 / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology; D019013:CD40 Antigens / Q000032:analysis / Q000235:genetics; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D003864:Depression, Chemical; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D007943:Leukemia, Hairy Cell; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D018951:Antigens, CD20; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins