FcγRIIb on liver sinusoidal endothelium clears small immune complexes

It has long been known that the ITIM-bearing IgG Fc receptor (FcγRIIb, RIIb) is expressed on liver sinusoidal endothelial cells (LSEC) and that the liver is the major site of small immune complex (SIC) clearance. Thus, we proposed that RIIb of LSEC eliminates blood-borne SIC, thereby controlling imm...

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Bibliographic Details
Published in:	The Journal of immunology (1950) 2012-11, Vol.189 (10), p.4981-4988
Main Authors:	Ganesan, Latha P, Kim, Jonghan, Wu, Yun, Mohanty, Sudhasri, Phillips, Gary S, Birmingham, Daniel J, Robinson, John M, Anderson, Clark L
Format:	Article
Language:	eng
Subjects:	Animals Antigen-Antibody Complex - genetics Antigen-Antibody Complex - immunology Chlorocebus aethiops COS Cells Endothelium - immunology Kupffer Cells - immunology Liver - immunology Male Mice Mice, Inbred BALB C Mice, Knockout Receptors, IgG - genetics Receptors, IgG - immunology
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Summary:	It has long been known that the ITIM-bearing IgG Fc receptor (FcγRIIb, RIIb) is expressed on liver sinusoidal endothelial cells (LSEC) and that the liver is the major site of small immune complex (SIC) clearance. Thus, we proposed that RIIb of LSEC eliminates blood-borne SIC, thereby controlling immune complex-mediated autoimmune disease. Testing this hypothesis, we found most RIIb of the mouse, fully three-quarters, to be expressed in liver. Moreover, most (90%) liver RIIb was expressed in LSEC, the remainder in Kupffer cells. An absent FcRγ in LSEC implied that RIIb is the sole FcγR expressed. Testing the capacity of liver RIIb to clear blood-borne SIC, we infused mice intravenously with radio-iodinated SIC made of OVA and rabbit IgG anti-OVA. Tracking decay of SIC from the blood, we found the RIIb knockout strain to be severely deficient in eliminating SIC compared with the wild-type strain, terminal half-lives being 6 and 1.5 h, respectively. RIIb on LSEC, a major scavenger, keeps SIC blood concentrations low and minimizes pathologic deposition of inflammatory immune complex.
ISSN:	0022-1767 1550-6606