Immature B Cells in Bone Marrow Express Fas/FasL

Abstract

Negative selection is a process by which autoreactive lymphocytes are eliminated from the developing antigen receptor repertoire. The mechanisms regulating negative selection of immature B lymphocytes in the bone marrow are poorly elucidated. Human bone marrow cells were examined in order to investigate the presence of the members of the Fas (APO-1/CD95) system. Here we demonstrate the expression of Fas in immature B lymphocytes (CD10/CD19+/CD40+/sIg+), and the presence of Fas natural ligand (FasL) in CD19+ bone marrow cells. The observed expression of apoptosis-related molecules might indicate how negative selection of autoreactive B cells can occur in human bone marrow.

Trypanosoma cruziInfection Selectively Renders Parasite-Specific IgG+ B Lymphocytes Susceptible to Fas/Fas Ligand-Mediated Fratricide

“…However, this idea is now controversial, because several recent reports indicate that activated B cells can express FasL (3,(13)(14)(15)(16)(17). Furthermore, FasL expressed on B cells activated by S. mansoni soluble egg Ags is functional, because it is able to kill a Fas-bearing target cell line (4).…”

“…Fasdeficient lpr and FasL-deficient gld mice present generalized lymphoproliferation and produce autoantibodies resembling human systemic lupus erythematosus (12). Recent reports have demonstrated FasL expression on the B cell compartment (3,4,(13)(14)(15)(16)(17), but the functional role of this expression is a matter of controversy. In vivo experiments with mixed gld chimeras suggested that FasL controls the expansion of lymphocytes only when expressed on T cells (18).…”

Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL+T and B Cells during MurineSchistosoma mansoniInfection

“…Significantly, an in vivo role for B cellmediated apoptosis during infection was suggested by the increased CD4 ϩ T cell death following adoptive transfer of SEAstimulated, FasL-bearing B cells. Previous studies have shown that mitogen-activated B cells expressed surface FasL (16) and that FasL expression was detectable on B cells isolated from human tonsil and bone marrow (20,30). Recent studies have demonstrated Epstein-Barr virus-and lectin-inducible FasL expression on B cells (8,34).…”

“…Inducible expression of FasL has generally been studied on T lymphocytes following activation by mitogens or through the T cell receptor complex (21). However, several recent reports indicate that activated B cells can express functional FasL (8,16,30,34). Susceptibility to FasL-mediated apoptosis is determined by the expression of the death receptor, Fas (CD95, Apo1), and by the activation state of the target cell (29).…”

Killer B lymphocytes: the evidence and the potential

“…Several other studies have demonstrated the expression of FasL on B cells freshly isolated from human lymphoid organs [40, 68, 87]. In one of these studies, expression of FasL was low in the thymus and most lymph nodes, but was detected in the spleen, tonsil and mucosal-associated lymphoid tissue, primarily on Ig + plasma cells [87].…”