Modulation of the Antibody Response to Sheep Red Blood Cells in Normal and Immunodeficient XID Mice by myo -Inositol

Abstract

Over the dose ranges tested, dietary vitamin A and myo-inositol induce similar changes in murine fetal growth and development. Because vitamin A is also known to affect the immune response, studies were conducted to determine if dietary myo-inositol might have an effect on antibody production. It was found that in vivo in inbred mice myo-inositol (4 mg/g of diet) accelerated the rate of appearance of plaqueforming cells (PFC) in a primary response to sheep red blood cells (SRBC). In vitro, myo-inositol accelerated the rate of appearance of colonies of anti-SRBC PFC (foci) and significantly increased the number of PFC per colony, but did not affect the number of foci per culture noted at the end of the culture period. myo-inositol had no effect on the PFC IgM:IgG ratio following a single exposure to the agent, but exposure to myo-inositol in vivo and in vitro resulted in a decrease in the number of IgM PFC per focus in a primary response and IgM and IgG PFC per focus in a secondary response. Based on studies suggesting that myo-inositol or a phosphorylated metabolite might act downstream from Bruton's tyrosine kinase (Btk) in a signal transduction pathway in B cells, immunodeficient CBA/CaHN-XID/J mice were fed a standard diet or the same diet supplemented with 0.4% myo-inositol. Mice given the supplemented diet produced significantly more IgM anti-SRBC antibody than did XID mice given the control diet (4.3 ± 2.5 vs 1.7 ± 2.8, 1/log₂), and produced approximately the same amount as immunocompetent controls (2.9 ± 0.9). When rechallenged with SRBC, XID mice given supplemental inositol produced significantly more IgM antibody than did the XID and immunocompetent controls (3.6 ± 0.5 vs 1.8 ± 1.1 and 1.5 ± 0.7, respectively). Added dietary inositol did not have a significant effect on primary or secondary IgG responses to SRBC, which remained impaired. These results suggest that dietary myo-inositol or a derivative may be able to modulate B-cell IgM responses by interacting within the inositol second messenger system downstream from Bruton's tyrosine kinase.