Sclerostin Deficiency Alters Peripheral B Lymphocyte Responses in Mice

Chow, A.; Mason, J.; Coney, L.; Bajwa, J.; Zaslavsky, A.; Pellman, Y.; Garcia-Ojeda, M. E.; Economides, A.; Loots, G.; Manilay, J. O.

doi:10.1101/357772

bioRxiv · 10.1101/357772

Sclerostin Deficiency Alters Peripheral B Lymphocyte Responses in Mice

Chow, A.·Mason, J.·Coney, L.·Bajwa, J.·Zaslavsky, A.·Pellman, Y.·Garcia-Ojeda, M. E.·Economides, A.·Loots, G.·Manilay, J. O.

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Abstract

Understanding how changes in bone physiology and homeostasis affect immune responses will inform how to retain strong immunity in patients with bone disease and in aged individuals. We previously identified sclerostin (Sost) as a mediator of cell communication between the skeletal and the immune system. Elevated bone mineral density in Sost-knockout (Sost-/-) mice contributes to an altered bone marrow microenvironment and adversely affects B cell development. B cells originate from hematopoietic stem cells within the bone marrow and mature in peripheral lymphoid organs to produce antibodies in response to infection and/or vaccination. In this study, we investigated whether the aberrant B cell development observed in the bone marrow of Sost-/- mice extends to peripheral B cells in the spleen during immune challenge, and if these changes were age-dependent. Concomitant with more severe changes in bone architecture, B cell development in the bone marrow and in the spleen worsened with age in Sost-/- mice. B cell responses to T-independent antigens were enhanced in young Sost-/- mice, whereas responses to T-dependent antigens were impaired. Our results support the hypothesis that the adverse effects of B cell development in the Sost-deficient bone marrow microenvironment extends to the peripheral B cell immune response to protein antigens, and suggest that the B cell response to routine vaccinations should be monitored regularly in patients being treated with sclerostin antibody therapy. In addition, our results open the possibility that Sost regulates the T-independent B cell response, which might be applicable to the improvement of vaccines towards non-protein antigens.

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Chow, A., Mason, J., Coney, L., Bajwa, J., Zaslavsky, A., Pellman, Y., Garcia-Ojeda, M. E., Economides, A., Loots, G., Manilay, J. O.. 2018-06-28. Sclerostin Deficiency Alters Peripheral B Lymphocyte Responses in Mice. https://doi.org/10.1101/357772

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