Latent membrane protein 2A, a viral B cell receptor homologue, induces CD5+ B-1 cell development.
The latent membrane protein 2A (LMP2A) of EBV plays a key role in regulating viral latency and EBV pathogenesis by functionally mimicking a constitutively active B cell Ag receptor. When expressed as a B cell-specific transgene in mice, LMP2A drives B cell development, resulting in the bypass of normal developmental checkpoints. In this study, we have demonstrated that expression of LMP2A in transgenic mice results in B cell development that exclusively favors B-1 cells. This switch to B-1 cell development occurs at the pre-B-cell stage of normal B cell development in the bone marrow, a B cell stage much earlier than appreciated for B-1 commitment. This finding indicates that all pre-B cells have the capacity to assume a B-1 cell phenotype if they encounter the appropriate signal during normal development. Furthermore, these studies offer insight into EBV latency and pathogenesis in the human host.
Ikeda
Akiko
A
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Merchant
Mark
M
Lev
Lori
L
Longnecker
Richard
R
Ikeda
Masato
M
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D004792:Enzyme Precursors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D051917:Leukosialin; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000172:deficiency; D017455:Receptors, IgE / Q000172:deficiency; D012795:Sialoglycoproteins / Q000096:biosynthesis; D040681:Structural Homology, Protein; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D017735:Virus Latency / Q000276:immunology
D015703:Antigens, CD; D015415:Biomarkers; D018956:CD5 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D004792:Enzyme Precursors; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D051917:Leukosialin; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D014763:Viral Matrix Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D013755:Tetradecanoylphorbol Acetate