Expression of functional activating and inhibitory Fcγ receptors on human B cells

Background: The CD32 (FcgammaII) receptor is involved in the regulation of the B cell response to antigen. The sole Fc receptor demonstrated in mice is the inhibitory FcgammaIIB receptor. Crosslinking this receptor does not lead to downstream signaling or cell activation. Instead, when immune complexes bind to Fcy on murine B cells, cell activation through the B cell antigen receptor is attenuated. The objective of this study was to evaluate the expression of the FcgammaII receptor and the response to immune complex stimulation in human B cells. Methods: Human lymphoblastoid, peripheral and tonsillar B cells were stained with anti-CD32 antibodies IV. 3 and 8.26 to determine the relative expression of the activating (FcgammaIIA) and inhibitory (FcgammaIIB) isoforms of CD32. Tetanus immune complexes were added to B cells and the activation of c-Jun amino-terminal kinase was assayed. Results: Unlike murine cells, human B cells express high levels of the activating form of the Fcgamma receptor IIA. Addition of immune complexes to peripheral B cells resulted in signaling of Jun kinase, an important downstream kinase involved in the regulation of B cell function. The level of expression of FcgammaIIA on human B cells was not uniform, but depended on activation status. Peripheral blood B cells expressed high levels of FcgammaIIA, while tonsillar B cells predominantly expressed FcgammaIIB. Furthermore, when peripheral B cells were activated, the expression of FcgammaIIA relative to FcgammaIIB decreased. Conclusion: The response of human B cells to binding of immune complexes depends on the relative expression of activating ( FcgammaIIA) versus inhibitory (FcgammaIIB) receptors. Copyright (C) 2004 S. Karger AG, Basel.