Subject: Scientists Find Gene That Triggers Formation of Different Antibodies 
Date: Published: 12/22/89 (85 lines)
Source:  Wall Street Journal.  Copyright Dow Jones & Co. Inc. 

    Technology & Medicine:
    Scientists Find Gene That Triggers
    Formation of Different Antibodies
    ----
    By David Stipp
    Staff Reporter of The Wall Street Journal

    CAMBRIDGE, Mass.  -- Scientists here identified a gene that
 triggers the immune system's formation of different
 antibodies, a milestone in immune research.
    The finding sheds light on how the immune system responds
 to a myriad of different invading microbes, which has been
 "one of the great mysteries of biology," said David
 Baltimore, a Nobel laureate who directed the research at the
 Whitehead Institute of Biomedical Research, which is
 affiliated with Massachusetts Institute of Technology.
    While the discovery probably won't have near-term medical
 uses, the newly found gene provides a broadly useful tool for
 studying immune functions in infectious diseases and other
 disorders.
    The discovery concerns the process by which immune cells
 make antibodies, Y-shaped molecules that float in the blood
 looking for foreign microbes.  The prongs of each antibody are
 shaped to fit a molecule on the surface of a specific
 invading micro-organism.  Once an antibody latches onto a
 microbe, it attracts other immune molecules that destroy the
 invader.
    The latest discovery builds on two previous findings.  In
 the 1970s, researchers discovered that immune cells called B
 cells combine a relatively small set of genes in different
 ways to create the genetic codes needed for millions of
 different antibody shapes.  More recently, scientists found
 that immune cells called T cells employ a similar
 gene-shuffling process to make antibody-like molecules,
 called receptors, that they use to recognize foreign
 invaders.
    Now the Whitehead researchers have found that in both
 cases, the gene shuffling is activated by a single genetic
 master switch, which they isolated and named recombination
 activating gene No. 1, or RAG-1.  The gene "is at the very
 heart of what makes the immune system go," said David G. 
 Schatz, co-author of the study, which is reported in today's
 issue of the journal Cell.  The researchers still don't know,
 however, whether RAG-1 triggers gene-shuffling directly or
 acts through intermediary genes.
    But with RAG-1 in hand, researchers can probe for gene
 recombination in different tissues.  Cells in the olfactory
 system, for example, may shuffle genes to create many
 receptors for recognizing different odor molecules.
    By blocking RAG-1, scientists may be able to produce
 immune defects in animals that would elucidate similar
 defects in human diseases, said Marjorie A. Oettinger,
 another author of the study.  The RAG-1 finding also may help
 researchers devise better ways to bolster the immune system
 in diseases such as acquired immune deficiency syndrome.
    Separately, researchers at the Whitehead Institute and at
 Johns Hopkins University reported that a previously
 discovered protein made by the AIDS virus may play an
 unexpected role in the disease's immune suppression.
    The finding concerns the transactivator, or TAT gene, of
 the AIDS virus.  Scientists earlier discovered that it
 amplifies production of the AIDS virus within infected cells.
 In the latest finding, researchers found that the protein
 made by the gene may have a second, more direct damaging
 effect on the immune system.
    In test-tube studies, they showed that the protein
 lessened the ability of infection-fighting white blood cells
 to respond to invading microbes.  "We think this is
 potentially very important to the process of the disease,"
 said Alan D. Frankel, a Whitehead researcher and co-author of
 the study, which is reported in today's issue of the journal
 Science.  He cautioned, however, that the TAT protein's immune
 suppression hasn't yet been established in animal or human
 studies.  Moreover, the AIDS virus is known to damage the
 immune system in other ways, mainly by destroying a crucial
 subset of white blood cells called T4 cells.

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