Somatic diversification of B cells: a role for autoreactive T lymphocytes

Although the immune system discriminates self from non-self, and autoreactivity has pathologic consequences, lymphocytes do recognize self antigens. Self-recognition involves immunoglobulin variable (Ig V) regions and major histocompatibility complex (MHC)-encoded molecules. Jerne postulated that recognition of self-idiotypes within an immune system was a necessary homeostatic mechanism, important in the regulation of the immune system both in the presence and absence of perturbation by exogenous antigen'. Support for this hypothesis has accumulated from a variety of experimental systems but the significance of autoreactive T lymphocytes which recognize MHC-encoded class II (Ia) molecules(2-5) remains unknown. Rosenberg et al. s have proposed that autoreactive T cells are involved in mediating autoimmunity when the mechanisms controlling theirfunction degenerate. Here Ronald Corley suggests that autoreactive T lymphocytes are responsible for the expansion and somatic diversification of the B-cell compartment from germ-line encoded V genes. Furthermore, he proposes that autoreactive T cells do not function autonomously but that B-cell activation follows occupation of the two relevant triggering molecules on the B-cell membrane, namely Ia molecules by the autoreactive T cells and surface immunoglobulin by internally complementary idiotypes.