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Current Trends in Immunology   Volumes    Volume 7 
Abstract
Dual regulatory mechanisms of B cell growth signaling by CD72
Nobumichi Hozumi
Pages: 161 - 169
Number of pages: 9
Current Trends in Immunology
Volume 7 

Copyright © 2006 Research Trends. All rights reserved

ABSTRACT

B cell antigen receptor (BCR)-mediated signaling is modulated positively and negatively by co-receptors expressed on the membrane surface of B cells. CD72 carrying two ITIMs is of particular interest, since this receptor may deliver both positive and negative signals. Cross-linking of CD72 activates B cells and rescues them partially from apoptosis, suggesting that the receptor-mediated signaling mechanism transmits a positive signal for B cell growth. On the other hand, B cells from CD72-deficient (CD72-/-) mice are hyper-responsive to BCR stimulation, suggesting that CD72 delivers a negative signal. SHP-1 and Grb2 bind to phosphorylated ITIM1 and ITIM2, respectively. We have established pre-B cell lines from CD72 -/- mice after J2 virus infection. These B cell lines were infected with retroviral vectors carrying mutations in the ITIMs of CD72. A series of experiments with these cell lines suggested that ITIM1/SHP-1 delivers a very strong negative signal that is down-regulated by signals through ITIM2/Grb2, leading to delivery of an attenuated negative signal. Cross-linking of CD72 leads to dephosphorylation of the ITIMs, resulting in the manifestation of an ostensible positive signal. The two contradictory mechanisms involved in B cell growth regulation by CD72 can be reconciled by the hypothesis that CD72 transmits a weakened negative signal regulating the B cell growth response.

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