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

Victoria L. Palmer, Razia Aziz-Seible, Michele D. Kassmeier, Mary Rothermund, Greg A. Perry, Patrick Swanson

Research output: Contribution to journalArticle

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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 Vk-Jk rearrangement associated with VprBP insufficiency in B cells and substantially rescues maturation of marginal zone and Igλ+ B cells, but not Igk+ B cells. In this background, expression of a site-directed Igk L chain transgene increases Igk+ 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 Igk editor L chains typically arising through secondary Igk rearrangement, but not selection of Igl 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 Igk+ 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.

Original languageEnglish
Pages (from-to)1524-1537
Number of pages14
JournalJournal of Immunology
Volume195
Issue number4
DOIs
StatePublished - Aug 15 2015

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B-Lymphocytes
Transgenic Mice
B-Lymphoid Precursor Cells
Ubiquitin-Protein Ligases
Transgenes
Alleles

All Science Journal Classification (ASJC) codes

  • Immunology
  • Medicine(all)

Cite this

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. / Palmer, Victoria L.; Aziz-Seible, Razia; Kassmeier, Michele D.; Rothermund, Mary; Perry, Greg A.; Swanson, Patrick.

In: Journal of Immunology, Vol. 195, No. 4, 15.08.2015, p. 1524-1537.

Research output: Contribution to journalArticle

Palmer, Victoria L. ; Aziz-Seible, Razia ; Kassmeier, Michele D. ; Rothermund, Mary ; Perry, Greg A. ; Swanson, Patrick. / 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. In: Journal of Immunology. 2015 ; Vol. 195, No. 4. pp. 1524-1537.
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