Resting B cells as tolerogens in vivo but only for minor histocompatibility antigens: evidence for activation of resting B cells in vivo.
BACKGROUND
Small, resting B cells (rB cells) express major histocompatibility complex (MHC) class II molecules but not the putative costimulatory molecules, B7-1 (CD80) and B7-2 (CD86); they are classified as nonprofessional antigen-presenting cells. rB cells have been shown to be capable of anergizing T cells in vitro and inducing the prolonged survival of skin grafts mismatched for a single minor histocompatibility (miH) antigen, H-Y. The aim of this study was to investigate ability of rB cells to induce unresponsiveness to multiple miH and MHC antigens.


METHODS
Mice were pretreated with 1 x 10(7) donor rB cells 14 days before transplantation of cardiac grafts mismatched for either a single or multiple miH and/or MHC antigens in vivo.


RESULTS
rB cells induced indefinite prolongation of cardiac grafts mismatched for H-Y antigen (C57BL/10 male to female). Moreover, 50% of grafts mismatched for multiple miH antigens (C3H to CBA) were accepted indefinitely in recipients treated with donor rB cells. In marked contrast, when grafts were mismatched for either a single MHC class I antigen, Kb (CBK to CBA), or multiple MHC and miH antigens (C57BL/10 to C3H), pretreatment with rB cells did not prolong graft survival. To investigate why rB cells were ineffective tolerogens for grafts mismatched for MHC antigens, we examined the fate of the cells in vivo. We demonstrate that, after intravenous injection of rB cells, expression of B7-2 was induced within 24 hr.


CONCLUSIONS
These data suggest that rB cells may be less effective at inducing specific unresponsiveness to MHC antigens because of their rapid activation in vivo.
Niimi
M
M
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, England.
Roelen
D L
DL
Wong
W
W
Hara
M
M
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D005260:Female; D016027:Heart Transplantation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D007108:Immune Tolerance; D007519:Isoantigens / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens