Es. Sobel et al., T-B COLLABORATION FOR AUTOANTIBODY PRODUCTION IN LPR MICE IS COGNATE AND MHC-RESTRICTED, The Journal of immunology, 152(12), 1994, pp. 6011-6016
A central question in autoimmunity is the mechanism of T cell help for
autoantibody production. For responses to exogenous Ag, T-B collabora
tion is restricted by MHC class II molecules. To determine whether T c
ell help that leads to autoantibodies in murine SLE is also MHC-restri
cted, we have constructed bone marrow chimeras with Ig heavy chain (Ig
h) allotype- and I-A-congenic donor B6/Ipr mice and I-A-congenic recip
ients. Developing T cells were thus positively selected in the host th
ymus to interact with B cells bearing I-A of one haplotype or the othe
r. Additional control host mice were heterozygous for I-A expression,
allowing T helper cell selection for both I-A haplotypes. Five months
after reconstitution, serum total IgC2a, IgM, IgG2a antichromatin, and
IgM rheumatoid factor were quantitated by allotype-specific ELISA. Da
ta showed that whereas substantial numbers of B cells were present fro
m both donor strains in all mice, autoantibody production was overwhel
mingly from those donor B cells expressing the same I-A haplotype as t
he host. Sera from the I-A heterozygous control recipient group had ro
ughly equal quantities of autoantibodies of both allotypes, as expecte
d. The finding of MHC;class II restriction implies that the T cell hel
p that drives autoantibody production in Ipr mice is delivered through
cognate (cell-to-cell) interactions and not by soluble factors alone.