Low levels of IFN-gamma down-regulate the integrin-dependent adhesion of B cells by activating a pathway that interferes with cytoskeleton rearrangement.
In order to fully mature and participate in the humoral immune response, immature B cells must first migrate into specific areas in the spleen where they differentiate into mature cells. However, before their maturation in the spleen, immature B cells must be excluded from non-splenic secondary lymphoid organs where any antigen encounter would lead to the death of the cells because of the negative selection process. We have recently shown that immature B cells can actively exclude themselves from antigen-enriched sites by down-regulating their integrin-mediated adhesion in a process mediated by interferon-gamma (IFN-gamma). In this study, we followed the pathway by which IFN-gamma regulates the homing of B cells. We show here that the inhibitory signal of IFN-gamma is transmitted through the IFN-gamma receptor whose engagement leads to the activation of PI3K. This PI3K activation subsequently leads to the inhibition of PKCalpha phosphorylation and cytoskeleton rearrangement required for promoting integrin-mediated adhesion and migration of B cells.
Flaishon
L
L
Department of Immunology, The Weizmann Institute of Science, Herzel St., Rehovot 76100, Israel.
Lantner
F
F
Hershkoviz
R
R
Levo
Y
Y
Shachar
I
I
D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000199:Actins; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha