TY - JOUR
T1 - The pre-B cell receptor signaling for apoptosis is negatively regulated by FcγRIIB
AU - Kato, I.
AU - Takai, T.
AU - Kudo, A.
PY - 2002/1/15
Y1 - 2002/1/15
N2 - Many studies have shown that FcγRIIB is a negative regulator of B cell receptor signaling, and even though FcγRIIB is expressed through all developmental stages of the B cell lineage, its involvement in pre-B cell receptor (pre-BCR) signaling has not been examined. To investigate FcγRIIB function at the pre-B cell stage, we have established pre-BCR positive pre-B cell lines from normal mice and FcγRIIB-deficient mice, named PreBR and Fcγ-/-PreBR, respectively. These cell lines are able to differentiate into immature B cells in vitro by removal of IL-7. In PreBR, apoptosis was moderately induced by F(ab')2 anti-μ Ab, but not by intact anti-μ Ab. Phosphorylation of SH2-containing inositol 5-phosphatase (SHIP) and Dok, which are involved in FcγRIIB signaling, was induced by anti-μ cross-linking in PreBR. In contrast, apoptosis was strongly induced by both the F(ab')2 and intact anti-μ Abs in Fcγ-/-PreBR, and the level of phosphorylation of SHIP or Dok was much lower in Fcγ-/-PreBR than those observed in PreBR. Restoration of FcγRIIB to Fcγ-/-PreBR followed by anti-μ cross-linking blocked severe apoptosis, and up-regulated SHIP and Dok phosphorylation. The results demonstrate that FcγRIIB negatively regulates pre-BCR-mediated signaling for apoptosis.
AB - Many studies have shown that FcγRIIB is a negative regulator of B cell receptor signaling, and even though FcγRIIB is expressed through all developmental stages of the B cell lineage, its involvement in pre-B cell receptor (pre-BCR) signaling has not been examined. To investigate FcγRIIB function at the pre-B cell stage, we have established pre-BCR positive pre-B cell lines from normal mice and FcγRIIB-deficient mice, named PreBR and Fcγ-/-PreBR, respectively. These cell lines are able to differentiate into immature B cells in vitro by removal of IL-7. In PreBR, apoptosis was moderately induced by F(ab')2 anti-μ Ab, but not by intact anti-μ Ab. Phosphorylation of SH2-containing inositol 5-phosphatase (SHIP) and Dok, which are involved in FcγRIIB signaling, was induced by anti-μ cross-linking in PreBR. In contrast, apoptosis was strongly induced by both the F(ab')2 and intact anti-μ Abs in Fcγ-/-PreBR, and the level of phosphorylation of SHIP or Dok was much lower in Fcγ-/-PreBR than those observed in PreBR. Restoration of FcγRIIB to Fcγ-/-PreBR followed by anti-μ cross-linking blocked severe apoptosis, and up-regulated SHIP and Dok phosphorylation. The results demonstrate that FcγRIIB negatively regulates pre-BCR-mediated signaling for apoptosis.
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U2 - 10.4049/jimmunol.168.2.629
DO - 10.4049/jimmunol.168.2.629
M3 - Article
C2 - 11777955
AN - SCOPUS:0037080203
VL - 168
SP - 629
EP - 634
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -