Without genetic fine-tuning, antibodies would be relatively ineffective in finding a good match on the surface of viruses, parasites, and other potentially dangerous foreign pathogens. The findings also reveal the workings of a gene mutation process that can go awry, leading to the development of certain forms of cancer or allergic reactions.

HHMI investigator Frederick W. Alt at Children's Hospital in Boston and Harvard Medical School directed the studies. His team's findings explain the genetic line dance by which an otherwise generic immunoglobulin (Ig), or antibody, molecule acquires the genetic components that encode for the structural characteristics it needs to activate appropriate pathways to eliminate specific types of invaders, or antigens. The appropriate class of Ig can then mark invading cells for elimination by other cells of the immune system.

The researchers' findings are published in two articles in the online editions of Nature Immunology and Nature on April 7 and April 9, 2003, respectively. Alt's research team members include three current or former HHMI research associates, Jayanta Chaudhuri, Reiko Shinkura and Ming Tian.

The studies focus on how B cell lymphocytes, one of the major cell classes that are deployed in an immune response, assemble the genes that encode for the specific classes of Ig on their surface. Unlike other genes, which retain their integrity through each cell division, multiple segments of Ig genes from disparate parts of the chromosome mix together numerous times to provide a diverse repertoire of functional antibodies. Subsequently, a second form gene shuffling creates var
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
9-Apr-2003