HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ogilvy, S. Articles by Holmes, N. Search for Related Content PubMed PubMed Citation Articles by Ogilvy, S. Articles by Holmes, N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH

Either of the CD45RB and CD45RO Isoforms Are Effective in Restoring T Cell, But Not B Cell, Development and Function in CD45-Null Mice¹

Sarah Ogilvy^2,*, Christine Louis-Dit-Sully^3,, Joanne Cooper^*, Robin L. Cassady^*, Denis R. Alexander^* and Nick Holmes^4,

^* Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom; and Department of Pathology, University of Cambridge, Cambridge, United Kingdom

The protein tyrosine phosphatase CD45 is expressed as a series of isoforms whose tissue and differentiation stage specificity is broadly conserved in evolution. CD45 has been shown to be an important regulator of a variety of functions in many different hemopoietic lineages. We have chosen an in vivo genetic complementation strategy to investigate the differential functions between isoforms. In this study, we report the characterization of transgenic mice which express the isoforms CD45RO or CD45RB as their only CD45 molecules, at a variety of expression levels and in the majority of hemopoietic lineages. Both CD45RO and CD45RB isoforms reconstitute thymocyte development in a CD45-null mouse background when expressed above a threshold level. The resulting mature T cells populate the peripheral lymphoid organs where they are found at normal frequency. Both CD45RO and CD45RB isoforms also permit T cell function in the periphery, although the threshold for normal function here appears to be set higher than in the thymus. In contrast, neither isoform is capable of fully restoring peripheral B cell maturation, even at levels approaching those in heterozygous CD45^+/- mice in which maturation is normal. In vitro activation of B cells by Ag-receptor stimulation is only minimally complemented by these CD45RO and CD45RB transgenes. Our results suggest that CD45 isoforms play unique roles which differ between the T and B lineages.

This article has been cited by other articles:

				K. Parikh, S. Poppema, M. P. Peppelenbosch, and L. Visser Extracellular ligation-dependent CD45RB enzymatic activity negatively regulates lipid raft signal transduction Blood, January 15, 2009; 113(3): 594 - 603. [Abstract] [Full Text] [PDF]

				R. J. Salmond, L. McNeill, N. Holmes, and D. R. Alexander CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform Int. Immunol., July 1, 2008; 20(7): 819 - 827. [Abstract] [Full Text] [PDF]

				S. M. Jackson, N. Harp, D. Patel, J. Zhang, S. Willson, Y. J. Kim, C. Clanton, and J. D. Capra CD45RO enriches for activated, highly mutated human germinal center B cells Blood, December 1, 2007; 110(12): 3917 - 3925. [Abstract] [Full Text] [PDF]

				T. Moroy and F. Heyd The impact of alternative splicing in vivo: Mouse models show the way RNA, August 1, 2007; 13(8): 1155 - 1171. [Abstract] [Full Text] [PDF]

				S. R. J. Taylor, D. R. Alexander, J. C. Cooper, C. F. Higgins, and J. I. Elliott Regulatory T Cells Are Resistant to Apoptosis via TCR but Not P2X7 J. Immunol., March 15, 2007; 178(6): 3474 - 3482. [Abstract] [Full Text] [PDF]

				J. I. Elliott, A. Sardini, J. C. Cooper, D. R. Alexander, S. Davanture, G. Chimini, and C. F. Higgins Phosphatidylserine exposure in B lymphocytes: a role for lipid packing Blood, September 1, 2006; 108(5): 1611 - 1617. [Abstract] [Full Text] [PDF]

				R. Dawes, S. Petrova, Z. Liu, D. Wraith, P. C. L. Beverley, and E. Z. Tchilian Combinations of CD45 Isoforms Are Crucial for Immune Function and Disease J. Immunol., March 15, 2006; 176(6): 3417 - 3425. [Abstract] [Full Text] [PDF]

				M. C. Lopez and N. Holmes Phenotypical and functional alterations in the mucosal immune system of CD45 exon 9 KO mice Int. Immunol., January 1, 2005; 17(1): 15 - 25. [Abstract] [Full Text] [PDF]

				S. Boxall, T. Stanton, K. Hirai, V. Ward, T. Yasui, H. Tahara, A. Tamori, S. Nishiguchi, S. Shiomi, O. Ishiko, et al. Disease associations and altered immune function in CD45 138G variant carriers Hum. Mol. Genet., October 1, 2004; 13(20): 2377 - 2384. [Abstract] [Full Text] [PDF]

				E. Z. Tchilian, R. Dawes, L. Hyland, M. Montoya, A. Le Bon, P. Borrow, S. Hou, D. Tough, and P. C. L. Beverley Altered CD45 isoform expression affects lymphocyte function in CD45 Tg mice Int. Immunol., September 1, 2004; 16(9): 1323 - 1332. [Abstract] [Full Text] [PDF]

				H. E. Fleming, C. D. Milne, and C. J. Paige CD45-Deficient Mice Accumulate Pro-B Cells Both In Vivo and In Vitro J. Immunol., August 15, 2004; 173(4): 2542 - 2551. [Abstract] [Full Text] [PDF]