GERMINAL CENTER FORMATION, IMMUNOGLOBULIN CLASS SWITCHING, AND AUTOANTIBODY PRODUCTION DRIVEN BY NON ALPHA BETA T-CELLS/

The production of class-switched antibodies, particularly immunoglobul in (Ig)G1 and IgE, occurs efficiently in T cell receptor (TCR)alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthes is are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha -/- mice are reactive to a similar spectrum of self-antigen as that ta rgeted by autoantibodies characterizing human systemic lupus erythemat osus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cel l-mediated condition. To distinguish whether the development of autoan tibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and ''non-alpha/beta T'' cells, the phenotype has been reconstitute d by transfer of various populations of B and non-alpha/beta T cells i ncluding cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish th at the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/d elta T cells. This type of B-T collaboration sustains the production o f germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell. help may drive Ig synthesis and autoreactivity under various c ircumstances, especially in cases of alpha/beta T cell immunodeficienc y.