Regulation of B cell activation in autoimmune mice.

These studies explore the regulation of immunoglobulin production in autoimmune mice. B cells were transferred from normal or autoimmune mice into H-2 compatible xid recipients. When transferred to autoimmune-prone xid mice, cells from either donor produced significant levels of autoantibody. Cells from the same animals transferred to normal xid recipients produced little autoantibody. An ELISA spot assay was then used to study the development of B cell repertoires in autoimmune animals. Young lupus-prone mice developed repertoires in which B cells reactive with both conventional antigens and autoantigens were simulated to a similar degree, a finding consistent with the influence of polyclonal B cell activation. To examine the effect of exogenously administered immune activators on the development of B cell repertoires, normal DBA/2 mice were stimulated with LPS or goat anti-mouse IgD. This led to a quantitative increase in the number of Ig-secreting cells and expression of a repertoire similar to that present in autoimmune mice. Immunization with a specific antigen induced a repertoire skewed toward reactivity against that antigen which did not resemble that present in autoimmune mice. These findings are consistent with the view that polyclonal activation contributes to the production of autoantibodies in early murine lupus.