Regulators of the Immunoglobulin Class-Switch Pathway Identified

Molecular immunologists have identified a pathway that enables the process of immunoglobulin class-switch recombination (CSR) in B cells, a process that allows the immune system to adapt its response to specific pathogens.

CSR allows B cells to change the class of immunoglobulins they manufacture – from IgM to IgG, for example - without changing the specificity of the immune response. However, if CSR continues without suitable regulatory influences, the result may be autoantibodies that attack tissues and organs of the host.

In a recent paper published in the August 1, 2010, online edition of the journal Nature Immunology investigators at Mount Sinai School of Medicine (New York, NY, USA) reported results obtained by studying cells and tissues from immunodeficient patients and genetically engineered mice. They described the discovery of a TACI receptor modulated molecular pathway connecting a series of immune regulators, MyD88-IRAK1-IRAK4-TRAF6-TAK1, that mediated CSR.

"Our research shows that TACI and MyD88 are part of an immune circuit that bridges the innate and adaptive immune systems. This circuit makes our immune response more flexible, allowing a more effective generation of protective antibodies during infections,” said senior author Dr. Andrea Cerutti, professor of medicine at Mount Sinai School of Medicine. "Genetic defects of TACI and MyD88 cause immunodeficiencies characterized by recurrent, life-threatening infections. On the other hand, an abnormally strong TACI-MyD88 interaction may exacerbate autoimmune diseases like lupus or rheumatoid arthritis. Previous studies had suggested an involvement of TACI and MyD88 in lupus. Now that we have identified this interaction, we can figure out a way to inhibit it and prevent these diseases from getting worse.”

"Our discovery provides a novel specific target, the signaling pathway between TACI and MyD88, to block the overreaction of the immune system and tissue damage in individuals with autoimmune disorders,” said Dr. Cerutti. "We look forward to studying this discovery further and developing therapeutic targets that will inhibit the interaction between TACI and MyD88, preventing autoimmune diseases from progressing with fewer side effects than currently prescribed treatments.”

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Mount Sinai School of Medicine