lpr, a murine mutation of the Fas apoptosis receptor, causes lymphaden
opathy and autoantibody production, with lymphadenopathy primarily due
to a population of CD4(-)CD8(-)B220(+) T cells, Previous in vice expe
riments, in which lpr and normal bone marrow cells were coinfused into
lpr hosts, have demonstrated that only T cells of lpr origin accumula
ted abnormally and only B cells of lpr origin produced autoantibodies.
Moreover, in these chimeras, B cells of normal origin were unable to
respond to conventional, T cell-dependent exogenous Ag, To address the
role of lpr B cells in regulation of lpr autoimmunity, we have prepar
ed lpr-+ mixed chimeras and selectively eliminated lpr B cells using a
llele-specific, mAb treatment, thus allowing normal B cells to develop
in an environment with lpr T tells, From these data, we arrived at fo
ur major conclusions: I) Compared with control-treated chimeric mice,
lpr B cell-depleted mice! had greatly reduced total lymph node cell co
unts; 2) the T cells were derived equally from normal and lpr donors,
and the percentage of lpr-derived CD4(-)CD8(-) T cells was greatly red
uced; 3) despite the presence of the remaining lpr T cells, no autoant
ibodies were produced by the normal derived B cells; and 4) lpr T cell
s without lpr B cells were unable to prevent a normal B cell response
to conventional Ag, These data demonstrate that B cells can play a cri
tical and expansive regulatory role, not only for T cells, but for oth
er B cells as well.