MODULATION OF B CELL RESPONSES BY NATURAL KILLER CELLS

  • Katz, Paul, (PI)

Project: Research project

Description

The natural killer (NK) cell system in man is an important component of th
immune surveillance network in which a specific subpopulation of
lymphocytes can destroy virus-infected cells, tumor cells, and heterologous
tissues. Additionally, data have now accrued which indicate that NK cells
may also display non-lytic immunoregulatory functions. Recent studies in
murine and human systems have shown that populations of lymphocytes
containing NK cells can suppress B lymphocyte proliferation and
immunoglobulin (lg) production in T cell-dependent systems. However, these
studies have not utilized purified populations of NK cells nor have they
examined the activity of NK cell subsets. Additionally, there has been no
investigation of B cell function in non-T cell-dependent systems. Given the role of NK cells in immunity against tumors and the therapeutic
modulation of NK activity with biologic response modifiers such as
interferon, it will be extremely important to determine: 1) the
interrelationship between NK cell cytotoxic and immunoregulatory function;
2) the modulation of these activities; 3) the regulatory activities of NK
cell subsets; 4) the mechanism(s) of regulation; and 5) the NK regulatory
function in patients with abnormalities of NK cytotoxic function. To
determine these, three specific areas will be investigated. We will
ascertain if NK cells can alter B cell function indirectly in T
cell-dependent systems. For this, highly purified populations of NK cells
will be utilized in pokeweed mitogen-dependent systems of B cell
proliferation and lg production. Since all stages in the T
cell-independent B cell differentiation sequence can be assessed, we will
investigate the ability of NK cells to modulate the early and late steps in
this sequence. Given our preliminary data that NK cells can affect B cell
function, we will determine the mechanism of this activity (direct vs.
indirect; cytoxic vs. non-cytotoxic). These studies will also assess the
ability of NK cell subsets to act as modulators of B cell function through
the isolation of specific subpopulations of NK cells. Additionally,
subsets of NK cells will be isolated by cloning techniques and their
ability to affect these responses determined. Lastly, patients with known
NK cytotoxic defects (e.f., SLE, AIDS) will be assessed for NK
immunoregulatory abnormalities. These studies should increase our
knowledge of the roles, significance, and functional capabilities of normal
NK cells and the potential importance of these lymphocytes in diseases of
immunoregulation.
StatusFinished
Effective start/end date3/1/872/28/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Natural Killer Cells
B-Lymphocytes
Population
Pokeweed Mitogens
Organism Cloning
Cell Differentiation
Immunity
Neoplasms
Acquired Immunodeficiency Syndrome
Lymphocytes
Viruses
T-Lymphocytes

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)