Abstract 1488: B-cell Derived IgM and IgG Immunoglobulin Isotypes Modulate Intimal Thickening in Immune-deficient Mice
Background: We and other investigators have shown that B cells modulate intimal thickening and atherosclerosis, however it is not clear if the effect is via specific immunoglobulin production or other mechanism(s). Using a carotid cuff injury model in mice, we tested the role of immunoglobulin isotypes in modulating intimal thickening by
adoptive transfer of splenocytes from wild-type mice, or
direct administration of IgG or IgM, to immune-deficient Rag-1KO mice.
Methods and Results: Splenocytes from wild-type mice were isolated and adoptively transferred to Rag-1KO mice which were then subjected to carotid cuff arterial injury 48 hours after cell transfer. Mice were then euthanized 21 days after injury for histomorphometric analysis. Transfer of splenocytes to Rag-1KO mice resulted in increased serum IgM and IgG within 48 hours and both normalized by 21 days after injury. IgG1, 2a, 2b, and 3 isotypes all normalized. Intimal area (Table 1⇓) in Rag-1KO+splenocytes (n=13) decreased by 45% compared with Rag-1KO mice without cell transfer (N=10). To further differentiate the relative contribution of IgM or IgG in reducing neointima, additional groups of Rag-1KO mice were subjected to injury and given intravenous injections of pooled mouse IgG or IgM at a dose of 500 mcg/mouse every other day for the first week and twice weekly subsequently, until euthanasia at 21 days after injury. Both IgG (n=9) and IgM (n=5) treatment significantly reduced intimal thickening compared with untreated Rag-1KO mice (Table 1⇓). Immunoglobulin treatments did not affect splenic IFN-γ and IL-10 mRNA expression.
Conclusion: Our results indicate that B cells modulate intimal thickening through immunoglobulins. There does not appear to be any isotype specificity since both IgG and IgM reduced intimal thickening.