The effect of dosage, gestational age and splenectomy on anti-IgM interception of prenatal B-cell development in sheep

• Published in: Clinical & developmental immunology 2003-03, Vol.10 (1), p.19-26
• Main Authors: McCullagh, P, Press, C McL, McClure, S J, Larsen, H J, Landsverk, T
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Anti-Idiotypic - administration & dosage; Antibodies, Anti-Idiotypic - immunology; Antibodies, Monoclonal; Antigens, Differentiation, B-Lymphocyte - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Dose-Response Relationship, Immunologic; Female; Fetus - immunology; Gestational Age; Immunoglobulin M - immunology; Immunohistochemistry; Peyer's Patches - immunology; Pregnancy; Sheep - embryology; Sheep - immunology; Splenectomy - adverse effects; Splenectomy - veterinary
• ISSN: 1740-2522; 2314-8861; 2314-7156; 1740-2530
• DOI: 10.1080/10446670310001598500

The administration of a single bolus of anti-IgM antibody to foetal lambs early in pregnancy produces prolonged B-cell depletion. The present study investigated this depletion by examining the effect, on B-cell development in the ileal Peyer's patches, of varying the timing and dosage of antibody administration and by supplementing anti-IgM with surgical splenectomy. The capacity of a 1 mg bolus of anti-IgM to deplete Peyer's patches of B cells was lost if its administration was deferred until two thirds of the way through pregnancy, but persisted beyond this time if weight-adjusted doses were used. Splenectomy of the foetus performed at an earlier age failed to extend the age at which a 1 mg dose of antibody remained effective. As the concentration of murine immunoglobulin in foetal serum was greatly reduced after 21 days, it is inferred that ongoing suppression of B-cell development is not dependent on the continued presence of murine immunoglobulin. The enduring nature of suppression could be attributable to a limited period during which differentiation of B cells from stem cells normally occurs, although further studies will be needed to investigate this and other possible explanations for the effect of anti-IgM treatment on prenatal B-cell development in sheep.