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 tumorspecific 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-2^d, Ig constant heavy chain allotype b (IgC_H^b) mice with the capacity to stimulate an I-A^d-restricted T cell clone which recognizes the γ2a^b 435–451 allopeptide. The corresponding self γ2a^a peptide is cryptic and 6000-fold less antigenic than the γ2a^b allopeptide. Even so, the syngeneic B cell lymphoma A20 which expresses surface (s) IgG2a^a, 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.