THE YAA GENE-MEDIATED ACCELERATION OF MURINE LUPUS - YAA(-) T-CELLS FROM NON-AUTOIMMUNE MICE COLLABORATE WITH YAA(-CELLS TO PRODUCE LUPUS AUTOANTIBODIES IN-VIVO() B)
L. Fossati et al., THE YAA GENE-MEDIATED ACCELERATION OF MURINE LUPUS - YAA(-) T-CELLS FROM NON-AUTOIMMUNE MICE COLLABORATE WITH YAA(-CELLS TO PRODUCE LUPUS AUTOANTIBODIES IN-VIVO() B), European Journal of Immunology, 25(12), 1995, pp. 3412-3417
The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune res
ponses in mice predisposed to lupus-like autoimmune disease. We have p
reviously shown that a cognate interaction of T cells with B cells exp
ressing the Yaa gene appears to be responsible for the accelerated pro
duction of autoantibodies. To investigate whether T cells that provide
help for autoantibody production by Yaa(+) B cells need to express th
e Yaa gene, we have made radiation bone marrow chimeras containing two
sets of T and B cells from mice with or without the Yaa gene and diff
ering by the Thy-1 and Igh allotypes. We then determined autoantibody
production following the selective elimination of T cells of Yaa(+) or
igin by treating mice with allele-specific anti-Thy-1 monoclonal antib
ody. Our results demonstrated that the selective production of autoant
ibodies by Yaa(+) B cells in Yaa(+)-Ya(-) double bone marrow chimeras
can be mediated as efficiently by T cells from non-autoimmune mice lac
king the Yna gene as by T cells from autoimmune mice bearing the Yaa g
ene. This indicates that T cells from nonautoimmune Yaa(-) mice are ca
pable of providing help for autoimmune responses by collaborating with
Yaa(+) B cells. These data thus strongly suggest that the Yna gene de
fect is not functionally expressed in T cells, but only in B cells, an
d contrast with parallel experiments in the Ipl model, in which defect
s of the Fas antigen in both T and B cells are crucial for the Ipl gen
e-mediated promotion of autoantibody production.