Enforced and prolonged CD40 ligand expression triggers autoantibody production in vivo.

Abstract

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.

• Authors: L Santos-Argumedo, I Alvarez-Maya, H Romero-Ramírez, L Flores-Romo
• Journal: European journal of immunology (Eur J Immunol) Vol. 31 Issue 12 Pg. 3484-92 (Dec 2001) ISSN: 0014-2980 [Print] Germany
• PMID: 11745368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• CD40 Antigens
• Histocompatibility Antigens Class II
• Immunoglobulin M
• Lipopolysaccharides
• Receptors, IgE
• CD40 Ligand

Topics

• Animals
• Apoptosis
• Autoantibodies (biosynthesis)
• B-Lymphocytes (immunology)
• CD40 Antigens (physiology)
• CD40 Ligand (physiology)
• Cells, Cultured
• Female
• Histocompatibility Antigens Class II (analysis)
• Immunoglobulin M (immunology)
• Lipopolysaccharides (pharmacology)
• Lymphocyte Activation
• Male
• Mice
• Mice, Inbred C3H
• Receptors, IgE (analysis)