AsianScientist (Apr. 24, 2011) – Researchers at the RIKEN Research Center for Allergy and Immunology (RCAI) have understood for the first time the mechanism governing differentiation of B cells into antibody-producing plasma cells.
In article in Science Signaling, they establish a role for the extracellular signal-regulated kinase (ERK) signaling pathway in B cell differentiation, a key step toward the development of B cell-targeted drugs for treatment of autoimmune diseases and allergies.
As the only cells in the body that produce antibodies, B cells play an essential role in the immune system’s defense against pathogens like bacteria and viruses. Differentiation of B cells into antibody-producing plasma cells is central to this role, initiating the production of antibodies which identify, bind to, and neutralize foreign objects.
The mechanism underlying this differentiation process, however, remains unknown.
To tease apart this signaling pathway, the research group focused on the signaling of the extracellular signal-regulated kinases (ERK), intracellular signaling molecules known to play an important role in the cell cycle and survival of immune cells.
Hoping to gain insights into the role of ERKs in B cell differentiation, the researchers generated mice deficient in two different ERKs, ERK1 and ERK2, and studied the effect of ERK deficiency on the fate of B cells.
They confirmed that ERKs are indeed essential to B cell differentiation: B cells in mice without these key molecules could not form plasma cells.
The researchers honed in on a gene called Prdm1 encoding the protein BLIMP-1, increased expression of which leads to differentiation and proliferation of plasma cells in B cell immune response. ERKs, they discovered, phosphorylate the transcription factor Elk1, which leads to Blimp-1 expression.
By understanding the role of ERKs in B cell differentiation, the current research provides valuable insight into this poorly-understood area, promising advances in drug discovery and offering hope to autoimmune disease and allergy sufferers worldwide.
The article can be found at: Yasuda T. et al. (2011) ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation.
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Source: RIKEN.
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