title: Regulatory role of CD95 ligation on human B cells induced in vivo capable of spontaneous and high-rate Ig secretion.
abstract: CD95 ligation elicits apoptotic signals in many cell systems. This study analyzes the effect of anti-CD95 mAb on human cells capable of spontaneous and high-rate Ig secretion. Such cells have been induced in vivo and represent a highly mature B cell stage. Addition of the anti-CD95 monoclonal antibody (mAb) CH11 to tonsil B cells inhibited 50-60% of their spontaneous Ig secretion. The effect was exerted early in the culture and could be reversed by a pre-treatment with a neutralizing mAb. N-acetyl-D-sphingosine (C2-ceramide), although not a close analog, also reduced Ig secretion to a similar extent. The inclusion of a tetrapeptide inhibitor for certain interleukin-1beta-converting enzyme proteases prevented the inhibitory effect of CH11 mAb on tonsil B cells. B cells capable of spontaneous Ab secretion obtained from blood of recently-immunized volunteers were also inhibited by CH11 mAb and C2-ceramide. In contrast, bone marrow (BM) B cells capable of spontaneous Ig secretion were unaffected by these agents. This CD95 ligation-mediated inhibition of tonsil and blood Ig-secreting B cells could not be reversed by cytokines with demonstrated activity on these B cells. Human mature B cells induced in vivo are identifiable as CD38hi cells. Flow cytometric analysis revealed that a fraction of tonsil CD38hi cells expressed low levels of CD95. Moreover, about 20% of these cells exhibited basal apoptosis, as defined by annexin V binding. This phenomenon was markedly increased by CD95 ligation. On the other hand, BM CD38hi cells showed neither CD95 expression nor CD95-induced annexin V binding. These data suggest that CD95 ligation might play a role in the control of human humoral responses by inducing apoptosis in susceptible mature B cells.
authors.affiliation: Servicio de Immunología, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Medina
authors.forename: C
authors.initials: C
authors.lastname: Segundo
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
authors.forename: J A
authors.initials: JA
authors.lastname: Brieva
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000921:Antibody-Producing Cells / Q000166:cytology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001854:Bone Marrow Cells; D020170:Caspase 1; D002454:Cell Differentiation; D002518:Ceramides / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D014066:Palatine Tonsil / Q000166:cytology; D011940:Receptor Aggregation; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D002518:Ceramides; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D019014:fas Receptor; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D003546:Cysteine Endopeptidases; D020170:Caspase 1