Transfer of endogenous retroviral superantigen from donor to recipient B cells following priming to induce peripheral T cell tolerance.
Endogenous retroviral superantigens such as vSAG-7 are highly stimulatory for T cells through interaction with the T cell receptor on the basis of V beta usage. Priming of adult MMTV 7-negative mice with vSAG-7-expressing cells has been shown to result in peripheral V beta 6/CD4+ T cell activation followed by tolerance to further interaction with the superantigen. The goal of the current study was to examine the cells presenting vSAG-7 during this initial burst of in vivo T cell activation. Priming of MMTV 7-negative BALB/c (H-2d) mice with DBA/2 (H-2d, MMTV 7+) spleen cells resulted in a 5- to 12-fold increase in the number of B cells in the lymph nodes. These B cells expressed increased levels of I-A and I-E class II MHC determinants. Use of MMTV 7-negative CB.17 (H-2d, Ighb) mice as recipients of DBA/2 (Igha) cells indicated that the increased number of B cells was of host, rather than donor, origin. The number of donor-derived (IgM/B220+) B cells observed during the course of vSAG-7-reactive V beta 6/CD4+ T cell activation was very low. Proliferation of unprimed T cells from MMTV 7-negative mice was induced during coculture with B cells from the lymph nodes of vSAG-7-primed recipients and was blocked by anti-class II MHC antibodies, as well as by an anti-vSAG-7 antibody. Highly purified host B cells from vSAG-7-primed recipients specifically stimulated the blastogenesis of V beta 6/CD4+ T cells in vitro. Collectively, the results indicate that following priming to induce peripheral tolerance, vSAG-7 is transferred from donor cells to class II MHC determinants on recipient B cells and is presented to the T cell repertoire by the autologous B cells.
Modlin
C S
CS
Department of Urology, Cleveland Clinic Foundation, Ohio 44195-0001, USA.
Todd
G T
GT
Cohen
T D
TD
Fairchild
R L
RL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens