ENGAGEMENT OF THE B-LYMPHOCYTE ANTIGEN RECEPTOR INDUCES PRESENTATION OF INTRINSIC IMMUNOGLOBULIN PEPTIDES ON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES

By means of the clonotypic variable region, the immunoglobulin (Ig) is a tumor-specific antigen on B cell neoplasms. We report that engageme nt of the B cell antigen receptor (BcR) promotes presentation of pepti des derived from the B cell's intrinsic Ig to major histocompatibility complex (MHC) class II-restricted T cells. Thus, anti-Ig endowed norm al, ex vivo B lymphocytes from H-2(d), Ig constant heavy chain allotyp e b (IgC(H)(b)) mice with the capacity to stimulate an I-A(d)-restrict ed T cell clone which recognizes the gamma 2a(b) 435-451 allopeptide. The corresponding self gamma 2a(a) peptide is cryptic and 6000-fold le ss antigenic than the gamma 2a(b) allopeptide. Even so, the syngeneic B cell lymphoma A20 which expresses surface (s) IgG2a(a), was also rec ognized by the T cells after BcR ligation. Thus, anti-Ig triggered the disclosure of a cryptic tumor antigen determinant. We propose that au toantigens, by engaging the BcR of self-reactive B cells, induce prese ntation of intrinsic Ig peptides to which the T helper cell (Th) reper toire is not tolerant. In this way, B cells with anti-self potential m ay be activated without Th recognition of nominal autoantigen.