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New Research on B Cells by NIH News Release
NIAID RESEARCHERS IDENTIFY
HIV-INDUCED CHANGES IN B CELLS
One of HIV's most insidious properties is its ability to
influence virtually every part of the human immune system.
Antibody-producing B cells, for example, begin to
malfunction early after people become infected with HIV,
for reasons that have been poorly understood. In a study
released August 14th, however, researchers identify specific
alterations that occur in B cells when HIV levels are high
-- changes that disappear when patients are treated with
antiretroviral drugs. The study, which appears in the
current "Proceedings of the National Academy of Sciences"
Early Edition online, is the first to define a unique
subset of B cells in people infected with HIV.
Anthony S. Fauci, M.D., director of the National Institute
of Allergy and Infectious Diseases (NIAID) and a principal
author of the paper, is all too familiar with HIV's effects
on his patients' immune systems. "Their B cells produce
excessive amounts of nonessential antibodies, fail to
respond properly to normal physiologic signals, and are at
increased risk of becoming cancerous," he explains.
"Because their B cells do not work properly, people with
HIV are left with fewer means to fight off the
opportunistic infections that we see in full-blown AIDS."
B cells produce antibodies, proteins that specifically
recognize and attach to foreign molecules, or antigens,
such as those found on the surface of an invading virus or
bacterium. Once they've hitched themselves to an antigen,
antibodies either directly block the microbe from spreading
or act as chemical beacons, signaling other immune system
components to eliminate the captured organism.
To learn how HIV affects B cells, researchers from Dr.
Fauci's laboratory studied the immune systems of people who
were infected with the virus. Susan Moir, Ph.D., Angela
Malaspina, Ph.D., and colleagues looked at B cells both
before and after patients were treated with antiretroviral
therapy. The researchers found consistent changes in B
cells that occurred when HIV levels in the blood were high.
"At high virus levels, people had a large number of totally
dysfunctional B cells," says Dr. Moir. "When we treated
the patients to reduce their virus levels, the B cells
reverted to their typical ways." When the researchers
analyzed the B cells in detail, they found a specific
change that might help explain the cells' loss of function:
decreased amounts of a protein called CD21.
CD21 is a molecule on the surface of B cells that attaches
to an immune system protein called complement. Dr. Moir
and colleagues studied the cells with low amounts of CD21
and found these cells were unable to respond to many
different B-cell stimuli in test tubes, yet spontaneously
produced large quantities of irrelevant antibodies. Both
of these properties are seen in the B cells of people with
HIV. The researchers had previously shown HIV can hitch a
ride on B cells by attaching to CD21, providing further
support for the protein's possible role in HIV-induced B-
cell malfunction (see news release).
"When we studied the cells further, they looked something
like plasma cells that couldn't quite make up their minds,"
says Dr. Moir. Plasma cells are B cells that, upon
recognizing an antigen, rapidly divide and pump out
thousands of antibody molecules to attack a microbial
invader. As B cells become plasma cells they change shape,
lose their CD21 and stop responding to many B cell
stimuli. "The B cells in patients with high virus levels
look like plasma cells under the microscope, have very
little CD21, and don't divide in response to chemical
signals," Dr. Moir continues, "but in other respects they
retain features of their parent B cells."
The researchers believe HIV causes changes to occur in B
cells that either partially transition them to plasma cells
or stimulate them to undergo changes along a completely
different biochemical pathway. By identifying a specific
change that links HIV levels with B-cell malfunction, Drs.
Moir, Malaspina and colleagues have a key tool to further
investigate how the virus is causing B cells to go awry.
"We know it happens, we know what drives it, and we know
what the consequences are," says Dr. Moir. "This is the
very first step in learning how we might be able to prevent
it and improve the care of people infected with HIV."
The study was funded by NIAID and the National Cancer
Institute (NCI). Researchers from NCI and the George
Washington University also assisted in the study.
NIAID is a component of the National Institutes of Health
(NIH). NIAID supports basic and applied research to
prevent, diagnose, and treat infectious and immune-mediated
illnesses, including HIV/AIDS and other sexually
transmitted diseases, tuberculosis, malaria, autoimmune
disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related
materials are available here.
Reference:
Moir S et al. HIV-1 induces phenotypic and functional
perturbations of B cells in chronically infected
individuals. This article is available on the "Proceedings
of the National Academy of Sciences" Web site (August 14
update). This article appears in the following topics:
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