γδ T Cells Shape Preimmune Peripheral B Cell Populations

Yafei Huang, Andrew Getahun, Ryan A. Heiser, Thiago O. Detanico, Katja Aviszus, Greg A. Kirchenbaum, Tamara L. Casper, Chunjian Huang, M. Kemal Aydintug, Simon R. Carding, Koichi Ikuta, Hua Huang, Lawrence J. Wysocki, John C. Cambier, Rebecca L. O’Brien, Willi K. Born

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Abstract

We previously reported that selective ablation of certain γδ T cell subsets, rather than removal of all γδ T cells, strongly affects serum Ab levels in nonimmunized mice. This type of manipulation also changed T cells, including residual γδ T cells, revealing some interdependence of γδ T cell populations. For example, in mice lacking Vγ4(+) and Vγ6(+) γδ T cells (B6.TCR-Vγ4(-/-)/6(-/-)), we observed expanded Vγ1(+) cells, which changed in composition and activation and produced more IL-4 upon stimulation in vitro, increased IL-4 production by αβ 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 γδ-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-Vγ4(-/-)/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 γδ T cells in this strain and on their enhanced potential of producing IL-4. Further evidence suggests the possibility of direct interactions between γδ T cells and B cells in the splenic MZ. Taken together, these data demonstrate the capability of γδ T cells of modulating size and productivity of preimmune peripheral B cell populations.
Original languageEnglish
Pages (from-to)217-31
Number of pages15
JournalJournal of Immunology
Volume196
Issue number1
Early online date18 Nov 2015
DOIs
Publication statusPublished - 1 Jan 2016

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