Differential inhibition of B-cell development and xenoreactive natural antibody production by administration of anti-mu or anti-delta monoclonal antibodies in adult rats.
BACKGROUND
Given the role of xenoreactive natural antibodies (XNA) in the pathogenesis of xenograft rejection, we tested whether the administration of anti-mu or anti-delta monoclonal antibodies (mAbs) in adult rats would suppress the generation of XNA.


METHODS
Adult LOU/C (Igkappa-1a) rats were treated with anti-mu or anti-delta mAbs after nonlethal total body irradiation and bone marrow transplantation from congenic LOU/C (Igkappa-1b) rats. The differentiation of donor bone marrow (BM)-driven Igkappa-1b+ B cells and XNA production were analyzed.


RESULTS
Both anti-mu and anti-delta mAbs arrested B-cell differentiation in the BM. In anti-mu-treated rats, there was a total depletion of donor-driven, peripheral Igkappa-1b+ B cells, secreting cells, and circulating XNA of the Igkappa-1b allotype. In anti-delta-treated rats, a significant number of Igkappa-1b+ B cells, which did not express membrane IgD, "escaped" deletion and partially repopulated peripheral lymphoid organs. This B-cell population was active in the production of XNA, as revealed by the high serum levels of XNA in these animals.


CONCLUSIONS
Anti-mu administration resulted in arrest of B-cell differentiation and in down-regulation of IgM and IgG XNA production in adult rats. These data suggest that the use of anti-mu mAbs may be a useful approach to suppress the production of XNA and prevent xenograft rejection. Furthermore, we suggest that the B-cell population responsible for the production of XNA in adult rats belongs to a B-cell lineage expressing low levels of membrane IgD and "escaping" deletion in the BM upon anti-delta treatment.
Experimental Immunology Unit, Faculty of Medicine, University of Louvain, Brussels, Belgium. MSOARES@bidmc.harvard.edu
M
M
Soares
X
X
Havaux
R
R
Van Beneden
I
I
Kinet
A A
AA
Chentoufi
F
F
Nisol
F
F
Cormont
H
H
Bazin
D
D
Latinne
D000818:Animals; D000910:Antibodies, Heterophile / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007138:Immunoglobulin delta-Chains / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000276:immunology*; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014183:Transplantation, Heterologous / Q000276:immunology*; D014916:Whole-Body Irradiation
D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D007126:Immunoglobulin Allotypes; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains