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Suppression of B-cell development as a result of selective expansion of
donor T cells during the minor H antigen graft-versus-host reaction
BA Garvy, JM Elia, BL Hamilton and RL Riley
Department of Microbiology and Immunology, University of Miami School of
Medicine, FL 33101.
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.
Volume 82,
Issue 9,
pp. 2758-2766,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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