AUTOREACTIVE T-CELLS WITH ATYPICAL MHC RESTRICTION FROM MRL-LPR/LPR MICE - FORBIDDEN CLONES REVISITED

  • 1 January 1988
    • journal article
    • research article
    • Vol. 4  (1) , 35-43
Abstract
MRL-lpr/lpr mice spontaneously develop a lethal form of systemic lupus erythematosus associated with massive lymphodenopathy, polyclonal B-cell activity, autoantibody production and antibody-dependent tissue injury. The sequence of events leading to B-cell proliferation and pathogenic autoantibody production are not clearly defined.sbd.abnormalities of both B and T cells have been observed. Isolation of individual T-cell clones would facilitate analysis of the cellular events involving both B and T cells that lead to autoantibody production. For this purpose, an autoreactive T-cell line (ARTC-I) was derived from the splenocytes of an unimmunized MRL-lpr/lpr mouse and maintained in culture by stimulation with syngeneic antigen presenting cells, without exogenous antigens. By T-cell receptor analysis it was demonstrated that ARTC-1 cells developed as a clone even through no attempt was made to clone them in vitro: Southern blot analysis of ARTC-l revealed a single rearrangement of the TcR .beta. chain locus with the other TcR .beta. chain gene remaining in the germline configuration. Northern blot analysis confirmed these findings and demonstrated that ARTC-l utilized C.beta.1 J.beta. 1.3 exclusively. ARTC-l had atypical MHC requirements for activation: antigen-presenting cells bearing both I-Ak and I-Ek major histocompatibility complex class II antigens were required for maximal proliferation of the ARTC-l clone. Activated ARTC-l secreted soluble factors that induced B-cell proliferation, immunoglobulin secretion, and anti-DNA antibody production. Unregualted cells of the AR-TC1 type could, therefore, lead to polyclonal B-cell activation and autoantibody production in vivo in the absence of exogeneous antigenic stimulation.