Differential inhibition of B-cell development and xenoreactive natural antibody production by administration of anti-mu or anti-delta monoclonal antibodies in adult rats.
(1998) Transplantation — Vol. 66, n° 3, p. 357-364 (1998)
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- 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.
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Soares, M., Havaux, X., Van Beneden, R., Kinet, I., Chentoufi, A. A., Nisol, F., Cormont, F., Bazin, H., & Latinne, D. (1998). Differential inhibition of B-cell development and xenoreactive natural antibody production by administration of anti-mu or anti-delta monoclonal antibodies in adult rats. Transplantation, 66(3), 357-364. https://doi.org/10.1097/00007890-199808150-00013 (Original work published 1998)