ANDROGENS EFFECTS ON B CELL DEVELOPMENT

Project: Research project

Project Details

Description

Mechanisms responsible for the female predominance of autoimmune
diseases remain obscure, but an important modulatory role for
gonadal steroid hormones is likely. We have found previously that
the thymus is an important target of androgen action within the
immune system, with attendant impact on peripheral T cell
immunity. The proposed studies aim to investigate how androgens
alter development of the other major compartment of the immune
system, B cells. We propose to investigate the mechanisms
underlying androgen-mediated effects of developing B cells. The
three specific aims of these studies are as follows: 1. The functional
significance of bone marrow target cells for androgen action will be
determined. The approach will utilize in vivo model of androgen
resistance, the testicular feminization (Tfm) mouse in bone marrow
transplantation experiments with normal C57 mice, resulting in
targeted expression of functional androgen receptors in either stromal
or lymphoid cells. Effects of androgen deprivation and replacement
on developing B cell subpopulations will be assessed. 2. The
physiologic processes mediated by androgens in the bone marrow
will be examined through studies of effects on cell cycling and
apoptosis. These studies will be done ex vivo using bone marrow
cells from animals which have undergone androgen manipulation and
in vitro in cultures of developing B cells. 3. The role of two
potential mediators of androgen actions on developing B cells,
transforming growth factor-beta and interieukin-7 (IL-7), will be
defined using in vitro models of B cell development. These studies
will elucidate how androgens directly alter development of B cells in
the bone morrow, and have potentially important implications of the
role of androgens in mechanisms underlying the female
predominance of autoimmune diseases.
StatusFinished
Effective start/end date9/30/979/29/98

Funding

  • National Institute of Allergy and Infectious Diseases

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