Either of the CD45RB and CD45RO isoforms are effective in restoring T cell, but not B cell, development and function in CD45-null mice.
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.
Ogilvy
Sarah
S
Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom.
Louis-Dit-Sully
Christine
C
Cooper
Joanne
J
Cassady
Robin L
RL
Alexander
Denis R
DR
Holmes
Nick
N
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004140:Dinitrophenols / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051567:Proto-Oncogene Proteins c-vav; D012710:Serum Albumin, Bovine / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D018797:Cell Cycle Proteins; D004140:Dinitrophenols; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D017493:Leukocyte Common Antigens