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 engagement of the B cell antigen receptor (BcR) promotes presentation of peptides derived from the B cell's intrinsic Ig to major histocompatibility complex (MHC) class II-restricted T cells. Thus, anti-Ig endowed normal, ex vivo B lymphocytes from H-2d, Ig constant heavy chain allotype b (IgCHb) mice with the capacity to stimulate an I-Ad-restricted T cell clone which recognizes the gamma 2ab 435-451 allopeptide. The corresponding self gamma 2aa peptide is cryptic and 6000-fold less antigenic than the gamma 2ab allopeptide. Even so, the syngeneic B cell lymphoma A20 which expresses surface(s) IgG2aa, was also recognized by the T cells after BcR ligation. Thus, anti-Ig triggered the disclosure of a cryptic tumor antigen determinant. We propose that autoantigens, by engaging the BcR of self-reactive B cells, induce presentation of intrinsic Ig peptides to which the T helper cell (Th) repertoire is not tolerant. In this way, B cells with anti-self potential may be activated without Th recognition of nominal autoantigen.