Gamma Delta T Cells Shape Preimmune Peripheral B Cell Populations

We previously reported that selective ablation of certain gamma delta T cell subsets, rather than removal of all TB T cells, strongly affects serum Ab levels in nonimmunized mice. This type of manipulation also changed T cells, including residual gamma delta T cells, revealing some interdependence of gamma delta T cell populations. For example, in mice lacking V gamma 4(+) and V gamma 6(+) gamma delta T cells (B6.TCR-V gamma 4(-/-)/6(-/-)), we observed expanded V gamma 1(+) cells, which changed in composition and activation and produced more IL-4 upon stimulation in vitro, increased IL-4 production by alpha beta T cells as well as spontaneous germinal center formation in the spleen, and elevated serum Ig and autoantibodies. We therefore examined B cell populations in this and other gamma delta-deficient mouse strains. Whereas immature bone marrow B cells remained largely unchanged, peripheral B cells underwent several changes. Specifically, transitional and mature B cells in the spleen of B6.TCR-V gamma 4(-/-)/6(-/-) mice and other peripheral B cell populations were diminished, most of all splenic marginal zone (MZ) B cells. However, relative frequencies and absolute numbers of Ab-producing cells, as well as serum levels of Abs, IL-4, and BAFF, were increased. Cell transfers confirmed that these changes are directly dependent on the altered gamma delta T cells in this strain and on their enhanced potential of producing IL-4. Further evidence suggests the possibility of direct interactions between gamma delta T cells and B cells in the splenic MZ. Taken together, these data demonstrate the capability of gamma delta T cells of modulating size and productivity of preimmune peripheral B cell populations.