Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction.
A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell-depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre-B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti-interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.
Garvy
B A
BA
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Elia
J M
JM
Hamilton
B L
BL
Riley
R L
RL
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D016026:Bone Marrow Transplantation; D006087:Graft vs Host Reaction; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*
D015851:Interleukin-7; D015778:Minor Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma