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Immune Regeneration Laboratory, Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Australia
A significant decline in immune function is characteristic of aging. Along with the involution of the thymus and associated impaired architecture, which contributes to profound loss of naive T cell production, there are also significant declines in B cell development and the progenitors that support lymphopoiesis. These collectively lead to a reduced peripheral immune repertoire, increase in opportunistic infections, and limited recovery following cytoablation through chemo- or radiotherapy. We have previously shown that sex steroid ablation (SSA) causes a major reversal of age-related thymic atrophy and improves recovery from hematopoietic stem cell transplant. This study focused on the impact of SSA on the B cell compartment and their progenitors in middle-aged and cyclophosphamide-treated mice. In both models, SSA enhanced the number of lymphoid progenitors and developing B cells in the bone marrow (BM) as well as reversing age-related defects in the cycling kinetics of these cells. Enhanced BM lymphopoiesis was reflected in the periphery by an increase in recent BM emigrants as well as immature and mature plasma cells, leading to an enhanced humoral response to challenge by hepatitis B vaccine. In conclusion, SSA improves lymphoid progenitor and B cell recovery from age- and chemotherapy-induced immunodepletion, complimenting the effects on T cells. Since SSA has been achieved clinically for over 25 years, this provides a novel, rational basis for approaching the need for immune recovery in many clinical conditions.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Norwood Immunology, the Australian Stem Cell Centre, and the National Health and Medical Research Council of Australia. J.A.D. was supported by a fellowship from the Cancer Council of Victoria.
2 J.A.D. and G.L.G. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Jarrod A Dudakov, Monash Immunology and Stem Cell Laboratories, Monash University, Wellington Road, Clayton, Victoria 3800, Australia. E-mail address: Jarrod.Dudakov{at}med.monash.edu.au
4 Current address: Allogeneic Hematopoietic Stem Cell Transplant Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
5 Abbreviations used in this paper: BM, bone marrow; CLP, common lymphoid progenitor; EPLM, early progenitor with lymphoid and myeloid potential; Cy, cyclophosphamide; SSA, sex steroid ablation; HBV, hepatitis B virus.
This article has been cited by other articles:
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  J. A. Dudakov, G. L. Goldberg, J. J. Reiseger, K. Vlahos, A. P. Chidgey, and R. L. Boyd Sex Steroid Ablation Enhances Hematopoietic Recovery following Cytotoxic Antineoplastic Therapy in Aged Mice J. Immunol., December 1, 2009; 183(11): 7084 - 7094. [Abstract] [Full Text] [PDF]
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