Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease.
Increased understanding of minor histocompatibility complex (MiHC) antigen presentation to donor T cells may permit methods to modulate graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT). Previously, we described the importance of B cells as antigen presenting cells in T cell responses to a virally induced murine leukemia. Using a B cell deficient mouse model in which mice receive either control rabbit immunoglobulin (RIgG) or rabbit anti-IgM mu chain from birth (B cell deficient), we evaluated whether B cells were necessary for T cell responses to MiHC and the induction of GHVD. Normal and B cell deficient C57BL/6 (H-2b) mice were primed with BALB.B (H-2b; MiHC incompatible) spleen cells and evaluated > 4 weeks later in vitro. While splenic or lymph node T cells obtained from BALB.B primed control C57BL/6 mice demonstrated strong in vitro proliferative responses to MiHC mismatched targets, B cell deficient hosts were markedly reduced to 14-42% of controls. Similarly, a strong MiHC specific cytolytic T cell response was observed in control C57BL/6 mice (53-100% specific cytotoxicity) whereas B cell depleted recipients had no activity (< or = 5% specific lysis). The role of B cells in GVHD was evaluated using a MiHC disparate mouse model (LP/J donor into C57BL/6 recipient). We found that 12% of B cell depleted recipient mice receiving B cell depleted donor cells developed GVHD compared to 50% of RIgG control mice. B cell depletion of donor cells only, resulted in a similar result with 0% of mice receiving B cell depleted donor cells developing GVHD compared to 38% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Schultz
K R
KR
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Paquet
J
J
Bader
S
S
HayGlass
K T
KT
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000502:physiology*; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000209:etiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D011817:Rabbits; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015778:Minor Histocompatibility Antigens