The human immunodeficiency virus (HIV) devastates the body's ability to
fight off infection by destroying a key class of T cells essential for
maintaining a vigorous immune response. Now, scientists from the National
Institute of Allergy and Infectious Diseases (NIAID) report for the first
time that B cells-the antibody-producing cells of the immune system-help
ferry HIV throughout the blood and can likely deliver the virus to nearby T
cells. This discovery, reported in the September 4 issue of the Journal of
Experimental Medicine, helps explain several phenomena associated with HIV
infection and paves the way for new approaches to eliminating the virus from
"This study enhances our understanding of how HIV persists in the body and
might partly explain the abnormalities seen in B-cell function in people
with HIV infection," says Anthony S. Fauci, M.D., NIAID director and chief
of the laboratory where the research took place. "Identifying this pool of
HIV-carrying cells also opens new avenues for treating the infection."
The research, conducted by Susan Moir, Ph.D., Angela Malaspina, Ph.D., and
colleagues from NIAID's Laboratory of Immunoregulation, follows reports from
several laboratories that HIV can infect B cells in the test tube and that
low levels of HIV genetic material can exist in B cells of HIV-infected
individuals. None of these reports, however, have identified viable HIV
associated with the B cells of infected individuals.
To address this concern, the researchers isolated B cells from the blood of
people with chronic HIV infection. When they examined these cells for the
presence of HIV, they found significant levels of the virus attached to the
surface of the cells. The scientists then used test-tube experiments to
show the virus could infect T cells under laboratory conditions.
Because of the close interaction between B and T cells in the immune system,
this discovery casts new light on how HIV can interact with T cells. The
two cell types constantly form temporary attachments with each other to
exchange information and coordinate the immune response. This gives the B
cells ample opportunity to pass HIV to previously uninfected T cells. Dr.
Moir explains that B cells are not a hidden reservoir of HIV, however,
because they do not house internalized, replicating virus, and the amount of
B-cell-bound virus decreases as HIV levels decline in the blood. "HIV does
not appear to reproduce inside B cells, but rather hitches a ride on the
cell surface so it is free to jump to nearby T cells."
The studies also might explain why B-cell-mediated immunity in individuals
with chronic HIV infections can go awry. "People with high levels of HIV in
the blood often have malfunctions in their B cell responses, such as
uncontrolled activation of antibody production," explains Dr. Moir. "In the
past, scientists have thought this was caused largely by indirect effects of
HIV infection, but now we have evidence that some B cell abnormalities might
be due to direct viral interference."
Dr. Moir and co-workers looked at the B cells carefully to determine how the
virus attached to the cells. They identified the docking point for HIV, a
molecule called CD21. This protein appears on the surface of B cells and
normally binds complement, a molecule that tags invading microbes and
targets them for destruction. The researchers discovered that HIV, when
attached to complement, could use CD21 as a binding site on the B cell.
Because complement normally "tickles" CD21, thereby signaling B cells to
produce antibodies, the scientists believe the uncontrolled production of
multiple antibodies in people with HIV might be caused by the repeated
stimulation of the B cell as the virus binds CD21.
Now that the researchers have shown how B cells might play a role in HIV
infection, they are testing to see if the HIV in infected T cells is
genetically related to that on the B cells. They are also pursuing more
studies on how HIV might directly cause deficiencies in B-cell function.
"Scientists haven't looked at B cells much during HIV infection," says Dr.
Moir, "This research opens a new opportunity for better understanding the
complex nature of the disease."
Scientists from the National Cancer Institute and Advanced BioScience
Laboratories, Inc., Kensington, Maryland, also participated in this study.