title: γδ T Cells Shape Preimmune Peripheral B Cell Populations.
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.
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Joint Laboratory for Stem Cell Engineering and Technology Transfer, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China;
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Andrew
authors.initials: A
authors.lastname: Getahun
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Heiser
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Thiago O
authors.identifier: http://orcid.org/0000-0001-9390-0072
authors.initials: TO
authors.lastname: Detanico
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Katja
authors.identifier: http://orcid.org/0000-0003-0036-8027
authors.initials: K
authors.lastname: Aviszus
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Greg A
authors.initials: GA
authors.lastname: Kirchenbaum
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Casper
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Chunjian
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: M Kemal
authors.initials: MK
authors.lastname: Aydintug
authors.affiliation: Institute of Food Research and Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7UG, United Kingdom; and.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Carding
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wysocki
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045; bornw@njhealth.org.
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018858:Germinal Center / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta; C505720:Tnfsf13b protein, mouse; D015847:Interleukin-4