T-B COLLABORATION FOR AUTOANTIBODY PRODUCTION IN LPR MICE IS COGNATE AND MHC-RESTRICTED

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.