γδ T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells

Abstract

Background: γδ T cells, like αβ T cells, are components of all well- studied vertebrate immune systems. Yet, the contribution of γδ T cells to immune responses is poorly characterized. In particular, it has not been resolved whether γδ cells, independent of any other T cells, can help B cells produce immunoglobulin and form germinal centers, anatomical foci of specialized T cell-B cell collaboration. Results: TCRβ(-/-) mice, which lack all T cells except γδ T cells, routinely displayed higher levels of antibody than fully T cell-deficient mice. Repeated parasitic infection of TCRβ(-/-) mice, but not of T cell-deficient mice, increased antibody levels and induced germinal centers that contained B cells and monoclonal γδ cells in close juxtaposition. However, antibody specificities were more commonly against self than against the challenging pathogen. γδ T cell-B cell help was not induced by repeated inoculation of TCRβ(-/-) mice with mycobacterial antigens. Conclusions: In the absence of any other T cells, γδ T cell-B cell collaboration can be significantly enhanced by repeated infection. However, the lack of obvious enrichment for antibodies against the challenging pathogen distinguishes γδ T cell help from αβ T cell help induced under analogous circumstances. The increased production of generalized antibodies may be particularly relevant to the development of autoimmunity, which commonly occurs in patients suffering from αβ T cell deficiencies, such as AIDS.