NDLI: VprBP Is Required for Efficient Editing and Selection of Igκ+ B Cells, but Is Dispensable for Igλ+ and Marginal Zone B Cell Maturation and Selection.

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VprBP Is Required for Efficient Editing and Selection of Igκ+ B Cells, but Is Dispensable for Igλ+ and Marginal Zone B Cell Maturation and Selection.

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VprBP Is Required for Efficient Editing and Selection of Igκ+ B Cells, but Is Dispensable for Igλ+ and Marginal Zone B Cell Maturation and Selection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Palmer, Victoria L. Kassmeier, Michele D. Perry, Greg A. Swanson, Patrick C. Aziz-Seible, Razia Rothermund, Mary
Description	Author Affiliation: Palmer VL ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178.); Aziz-Seible R ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178.); Kassmeier MD ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178.); Rothermund M ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178.); Perry GA ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178.); Swanson PC ( Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68178 pswanson@creighton.edu.)
Abstract	B cell development past the pro-B cell stage in mice requires the Cul4-Roc1-DDB1 E3 ubiquitin ligase substrate recognition subunit VprBP. Enforced Bcl2 expression overcomes defects in distal VH-DJH and secondary Vκ-Jκ rearrangement associated with VprBP insufficiency in B cells and substantially rescues maturation of marginal zone and Igλ(+) B cells, but not Igκ(+) B cells. In this background, expression of a site-directed Igκ L chain transgene increases Igκ(+) B cell frequency, suggesting VprBP does not regulate L chain expression from a productively rearranged Igk allele. In site-directed anti-dsDNA H chain transgenic mice, loss of VprBP function in B cells impairs selection of Igκ editor L chains typically arising through secondary Igk rearrangement, but not selection of Igλ editor L chains. Both H and L chain site-directed transgenic mice show increased B cell anergy when VprBP is inactivated in B cells. Taken together, these data argue that VprBP is required for the efficient receptor editing and selection of Igκ(+) B cells, but is largely dispensable for Igλ(+) B cell development and selection, and that VprBP is necessary to rescue autoreactive B cells from anergy induction.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1500952
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-lymphocytes Cytology Metabolism Carrier Proteins Genetics Cell Differentiation Clonal Selection, Antigen-mediated Immunoglobulin Kappa-chains Immunoglobulin Lambda-chains Alleles Animals Immunology Cell Membrane Clonal Anergy Gene Expression Gene Rearrangement, B-lymphocyte, Heavy Chain Interferon Regulatory Factors Mice Mice, Transgenic B-cell-specific Activator Protein Phenotype Proto-oncogene Proteins C-bcl-2 V(d)j Recombination Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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