B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice.
The Fas/Fas ligand (FasL) pathway is one of the two major effector mechanisms of T cell-mediated cytotoxicity. To prevent nonspecific killing by lymphoid cells, FasL expression on the cell surface of immune effector cells is strictly regulated. However, MRL/lpr autoimmune-prone mice massively overexpress FasL on their T lymphocytes, which render them able to kill Fas+ targets in vitro and in vivo. It is surprising that we show in the present work that B lymphocytes purified from MRL/lpr spleen cells express FasL to the same extent as T cells at the mRNA and protein level. These B cells are potent cytotoxic effectors against Fas+ but not Fas- targets. The B lymphocyte effectors were used ex vivo without any in vitro activation by B cell stimuli. Furthermore, we found that MRL/lpr B lymphocytes have the same cytotoxic potential as natural killer cells, which have been characterized as potent, Fas-mediated, cytotoxic effectors. The level of membrane-anchored FasL increases with the size of the B cell and cell-surface activation marker CD69 expression, indicating that the expression of FasL is up-regulated in parallel with the activation state of the B cell. The activated B cell population contained the major cytotoxic activity, and a minor part was associated with CD138/Syndecan-1+ plasma cells.
Bonardelle
Danielle
D
CNRS UPR 9045, Villejuif, France.
Benihoud
Karim
K
Kiger
Nicole
N
Bobé
Pierre
P
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors