Enforced and prolonged CD40 ligand expression triggers autoantibody production in vivo.
CD40, a glycoprotein expressed on B lymphocytes plays an important role in B cell development, growth and differentiation. The ligand for the CD40 is a 39-kDa glycoprotein (CD154) expressed on the surface of activated T lymphocytes and is essential for thymus-dependent humoral immunity. The expression of CD154 is tightly regulated and its transient expression reduces the chances of potentially deleterious bystander activation of B cells. Stimulation through CD40 has been studied in vitro by using antibodies against CD40, by membranes of activated T cells or lately, by CD154 transfected cells. In this work we have evaluated the outcome of CD40-CD40 ligand interaction in vitro and in vivo by using CD154-transfected L929 cells. In vitro assays showed that CD154-L929 cells can induce on B cells: IL-4-dependent proliferation, up-regulation of CD23, CD54 and class II molecules and can also rescue WEHI-231 B cell lymphoma from anti-IgM-induced apoptosis. Interestingly, in vivo assays revealed that when CD154-L929 cells were inoculated into the spleen, mice developed a strong but transient production of anti-erythrocyte autoantibodies. Through B lymphocyte activation with CD154-transfected L929 cells both in vitro and in vivo, our data reveal that enforced and prolonged expression of CD40 ligand overcomes the tightly regulated mechanisms of B cell activation, triggering the production of autoantibodies. This system might be used to evaluate the early steps of an autoimmune response and the role of CD40-CD154 in the induction of primary responses in vivo.
Santos-Argumedo
L
L
Department of Molecular Biomedicine, Centro de Investigación y Estudios Avanzados, México, Mexico. lesantos@mail.cinvestav.mx
Alvarez-Maya
I
I
Romero-Ramírez
H
H
Flores-Romo
L
L
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007075:Immunoglobulin M / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D017455:Receptors, IgE / Q000032:analysis
D001323:Autoantibodies; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D017455:Receptors, IgE; D023201:CD40 Ligand