Molecular Regulation of B Lymphocyte Response

Antibodies are one of the key elements in the immune system. On the one hand, they play an essential role in protection against viral and bacterial infections; on the other hand, they are involved in certain autoimmune diseases and in immediate-type hypersensivity. B cells are the only euka­ ryotic cells that can produce antibody molecules. The regulated production of antibody molecules is one of the most complex examples of eukaryotic cell differentiation and one of those most. amenable to scientific in­ vestigation. Since the discovery of T and B cell interaction in the antibody response, the mechanism of the regulatory function(s) ofT cells in the B cell response has been one of the central issues in immunology. The existence ofT cell­ derived helper factors that promote B cell proliferation and antibody secretion was recognized in the early and mid 1970s. Dutton and his colleagues (1) as well as Schimpl & Wecker (2) demonstrated that culture supernatants of murine T cells stimulated by mixed lymphocyte reaction or by T cell mitogens could reconstitute the antibody response of T cell­ depleted splenic lymphocytes. Kishimoto and his colleagues (3) showed that anti-immunoglobulin (anti-Ig) and T cell--wnditioned medium could induce Ig secretion in rabbit B cells, indicating that two totally antigen­ nonspecific signals (i.e. cross-linking Ig-receptors and T cell-derived helper factors) could induce Ig production in B cells. Subsequently, the results obtained with rabbit B cells were confirmed in the murine system. Parker and his colleagues (4) could induce Ig secretion in murine B cells with in solubilized anti-Ig and culture supernatants of concanavalin A (Con A)­ stimulated T cells. All of these results indicated that the helper function of T cells in antibody response was mediated by soluble factors.