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 language | English |
|---|---|
| Pages (from-to) | 1524-1537 |
| Number of pages | 14 |
| Journal | Journal of Immunology |
| Volume | 195 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 15 2015 |
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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 journal › Article
}
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
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
VL - 195
SP - 1524
EP - 1537
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -