Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice

W.J. de Jonge, K.L. Kwikkers, A. te Velde, S.J. van Deventer, M.A. Nolte, R.E. Mebius, J.M. Ruijter, M.C. Lamers, W.H. Lamers

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Abstract

Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice.

de Jonge WJ, Kwikkers KL, te Velde AA, van Deventer SJ, Nolte MA, Mebius RE, Ruijter JM, Lamers MC, Lamers WH.

Department of Anatomy and Embryology, University of Amsterdam, The Netherlands.

Apart from its role in the synthesis of protein and nitric oxide (NO), and in ammonia detoxification, the amino acid arginine exerts an immunosupportive function. We have studied the role of arginine in immune defense mechanisms in the developing postnatal immune system. In suckling mice, arginine is produced in the small intestine. In F/A-2(+/+) transgenic mice, which overexpress arginase in their enterocytes, circulating and tissue arginine concentrations are reduced to 30-35% of controls. In these mice, the development and composition of the T cell compartment did not reveal abnormalities. However, in peripheral lymphoid organs and the small intestine, B cell cellularity and the number and size of Peyer's patches were drastically reduced, and serum IgM levels were significantly decreased. These phenotypes could be traced to an impaired transition from the pro- to pre-B cell stage in the bone marrow. Cytokine receptor levels in the bone marrow were normal. The development of the few peripheral B cells and their proliferative response after in vitro stimulation was normal. The disturbance in B cell maturation was dependent on decreased arginine levels, as this phenotype disappeared upon arginine supplementation and was not seen in NO synthase- or ornithine transcarbamoylase-deficient mice. We conclude that arginine deficiency impairs early B cell maturation
Original languageEnglish
Pages (from-to)1539-1548
Number of pages10
JournalJournal of Clinical Investigation
Volume110
Issue number10
DOIs
Publication statusPublished - 1 Jan 2002

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