Long-term control of alloreactive B cell responses by the suppression of T cell help.
Alloantibodies can play a key role in acute and chronic allograft rejection. However, relatively little is known of factors that control B cell responses following allograft tolerance induction. Using 3-83 Igi mice expressing an alloreactive BCR, we recently reported that allograft tolerance was associated with the sustained deletion of the alloreactive B cells at the mature, but not the immature, stage. We have now investigated the basis for the long-term control of alloreactive B cell responses in a non-BCR-transgenic model of C57BL/6 cardiac transplantation into BALB/c recipients treated with anti-CD154 and transfusion of donor-specific spleen cells. We demonstrate that the long-term production of alloreactive Abs by alloreactive B cells is actively regulated in tolerant BALB/c mice through the dominant suppression of T cell help. Deletion of CD25(+) cells resulted in a loss of tolerance and an acquisition of the ability to acutely reject allografts. In contrast, the restoration of alloantibody responses required both the deletion of CD25(+) cells and the reconstitution of alloreactive B cells. Collectively, these data suggest that alloreactive B cell responses in this model of tolerance are controlled by dominant suppression of T cell help as well as the deletion of alloreactive B cells in the periphery.
Li
Yijin
Y
Department of Surgery, Section of Transplantation, University of Chicago, Chicago, IL 60637, USA.
Ma
Lianli
L
Yin
Dengping
D
Shen
JiKun
J
Chong
Anita S
AS
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D023201:CD40 Ligand / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*; D014184:Transplantation, Homologous
D007518:Isoantibodies; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand