Diaz edits special issue of the journal Autoimmunity
By Robin Arnette
Ever wonder why you don’t get as sick the second time you get a particular infection? The short answer is your body’s immune system has learned to recognize the pathogen and is able to mount a vigorous response the second time around. However, according to research performed by NIEHS researcher Marilyn Diaz, Ph.D., this process also increases the chance your immune cells will attack your own healthy cells, causing autoimmune disorders.
Diaz studies a set of immune cells, called B lymphocytes or B cells, and the small molecule they make called activation-induced deaminase (AID). Because of her expertise in the area, the editor-in-chief at the journal Autoimmunity asked her to edit a special issue on the topic. In addition to her editing duties for the 2013 March issue, she wrote the introduction and contributed a review article on the role of AID in lupus nephritis, an autoimmune disease of the kidney.
AID in autoimmunity
According to Diaz, B cells produce millions of antibodies the body uses to fight infection. Surprisingly, the origins of certain systemic autoimmune disorders may be traced to two pathways that take place during B cell development. In one, the body may normally produce B cells that recognize self-antigens in the bone marrow. Diaz said these cells are usually purged from the body, but sometimes this removal doesn’t occur.
“There’s a process in the bone marrow that prevents them from getting out and participating in an immune response,” Diaz said. “When that process breaks down, these autoreactive cells get out and mistakenly destroy the body’s cells.”
Diaz said the second route involves previously nonautoreactive cells becoming autoreactive. As B cells mature, they accumulate mutations in the genes that eventually encode the antibodies. These mutations are positively selected for their ability to recognize that pathogen, but these mutations may also accidentally enhance the B cell’s ability to recognize self-antigens. She explained that the molecule responsible for causing the mutations was AID.
“You cannot get the mutations that increase affinity to either self or foreign antigens without AID,” Diaz said, “and since AID is only expressed in B cells and has no other function than mutation and the generation of the different classes of antibodies like IgG, it has the potential to be a target for therapeutics.”
As a matter of fact, several pharmaceutical companies are exploring that possibility by developing AID inhibitors. It’s no wonder Diaz and other researchers in the field, not to mention the millions of people with autoimmune diseases, are excited by the prospects.
Wearing her editing hat
When Kyoto University’s Tasuku Honjo, Ph.D., discovered AID in 2000, Diaz said, immunologists around the world hailed it as a monumental find, because it identified the molecule responsible for improving B cell immune memory. Researchers didn’t zero in on AID’s connection to autoimmunity, though, until Diaz and a few other scientists started looking at it from that angle in 2006.
Her knowledge of the mechanisms of autoimmunity made Diaz an excellent choice as editor, but, she said, this journal issue will be important for other reasons.
“It introduces AID to the world as a potential focus for treating autoimmunity, and it would not have been possible if it weren’t for the high caliber of scientists who contributed articles,” Diaz added. “The issue will have an impact because of them.”