An important role of phospholipase Cgamma1 in pre-B-cell development and allelic exclusion.
Phospholipase Cgamma1 (PLCgamma1) has been reported to be expressed predominantly in T cells and to play an important role in T-cell receptor signaling. Here we show that PLCgamma1 is expressed throughout B-cell development, with high expression in B-cell progenitors, and is involved in pre-B-cell receptor (pre-BCR) signaling. Reduced expression of PLCgamma1, in the absence of PLCgamma2 (PLCgamma1+/-PLCgamma2-/-), impedes early B-cell development at the pro-B- to pre-B-cell transition and impairs immunoglobulin heavy chain allelic exclusion, hallmarks of defective pre-BCR signaling. In contrast, early B-cell development is largely normal, whereas late B-cell maturation is impaired in the absence of PLCgamma2 alone (PLCgamma2-/-) and overexpression of PLCgamma1 in PLCgamma2-/- mice fails to restore BCR-mediated B-cell proliferation and maturation. These studies reveal an essential role of PLCgamma1, distinct from that of PLCgamma2, in B-cell development.
Wen
Renren
R
The Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI 53226, USA.
Chen
Yuhong
Y
Schuman
James
J
Fu
Guoping
G
Yang
Shoua
S
Zhang
Weiguo
W
Newman
Debra K
DK
Wang
Demin
D
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000502:physiology*; D003433:Crosses, Genetic; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051966:Phospholipase C gamma; D010738:Type C Phospholipases / Q000172:deficiency* / Q000378:metabolism*
D010738:Type C Phospholipases; D051966:Phospholipase C gamma