TY - JOUR
T1 - 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
AU - Palmer, Victoria L.
AU - Aziz-Seible, Razia
AU - Kassmeier, Michele D.
AU - Rothermund, Mary
AU - Perry, Greg A.
AU - Swanson, Patrick C.
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2015/8/15
Y1 - 2015/8/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1500952
DO - 10.4049/jimmunol.1500952
M3 - Article
C2 - 26150531
AN - SCOPUS:84938941551
VL - 195
SP - 1524
EP - 1537
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -