AUTOIMMUNE NERVOUS SYSTEM DISEASE: B CELL REPERTOIRE

Project: Research project

Project Details

Description

A hallmark of autoimmune disease is an increase in the incidence of
self-reactive B lymphocytes with the subsequent production of
autoantibodies. It seems clear that regulatory defects are intimately
associated with the onset, if not the continuance, of autoimmunity. One
of the goals of the first phase of this proposal is to determine whether
or not there are alternations in the composition of the immune repertoire
in select autoimmune mouse strains which are potentially pathogenic to
nervous system (NS) tissues. We will evaluate the serum, CSF and brain
homogenates for autoantibodies of potential NS importance. We will also
examine the integrity of the blood-brain-barrier in individual mice.
Then we will examine the lymphoid and NS B cell repertoire and selection
of V gene families in these mice just prior to the onset of autoimmunity
and during the time of overt autoimmunity. This will be accomplished by
examining the characteristics of B cells to foreign haptens and self
antigens with potential NS importance and by examining B cells (both
stimulated and unstimulated) for V gene family expression with in situ
hybridization and polymerase chain reaction (PCR). The primary goal of
second phase of this proposal is to utilize the techniques learned and
information gained in order to analyze B lymphocyte specificity and
autoantibody production in human SLE patients. We will examine the
repertoire and selection of V gene families in the CSF B cells of human
SLE patients. This will be accomplished by evaluating paired sera and
CSF from individual patients for antibodies directed against important
self antigens; examining CSF derived B cells for antibody production
against self antigens using antigen and mitogen stimulated culture
techniques; examining these cells for V gene family expression using in
situ hybridization and V gene sequence using PCR techniques. The NS
function of these patients will be evaluated as well. Our approach of
asking specific questions about the degree of diversity and specificity
of the NS immune response involves a multifaceted evaluation of antigen
specificity and immunoglobulin gene family expression. The information
resulting from these studies will contribute significantly to our
understanding of immune regulation and NS pathology in SLE.
StatusFinished
Effective start/end date4/1/913/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health: $91,260.00
  • National Institutes of Health
  • National Institutes of Health: $87,623.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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