Allelic-dependent expression of an activating Fc receptor on B cells enhances humoral immune responses.
Allelic-dependent expression of an activating Fc receptor on B cells enhances humoral immune responses.
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DOI：
10.1126/scitranslmed.3007097
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发表时间：
2013-12-18
影响因子：
17.1
通讯作者：
Edberg JC
中科院分区：
文献类型：
--
作者：
Li X;Wu J;Ptacek T;Redden DT;Brown EE;Alarcón GS;Ramsey-Goldman R;Petri MA;Reveille JD;Kaslow RA;Kimberly RP;Edberg JC
B cells are pivotal regulators of acquired immune responses and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of B cell function can significantly alter immunological responses. The balance of negative and positive signals in maintaining an appropriate B cell activation threshold is critical in B lymphocyte immune tolerance and autoreactivity. FcγRIIb (CD32B), the only recognized Fcγ receptor on B cells, provides IgG-mediated negative modulation through a tyrosine-based inhibition motif which down-regulates B cell receptor initiated signaling. These properties make FcγRIIb a promising target for antibody-based therapy. Here we report the discovery of allele-dependent expression of the activating FcγRIIc on B cells. Identical to FcγRIIb in the extracellular domain, FcγRIIc has a tyrosine-based activation motif in its cytoplasmic domain. In both human B cells and in B cells from mice transgenic for human FcγRIIc, FcγRIIc expression counterbalances the negative feedback of FcγRIIb and enhances humoral responses to immunization in mice and to BioThrax® vaccination in a human Anthrax vaccine trial. Moreover, the FCGR2C-ORF allele is associated with the risk of development of autoimmunity in humans. FcγRIIc expression on B cells challenges the prevailing paradigm of uni-directional negative feedback by IgG immune complexes via the inhibitory FcγRIIb, is a previously unrecognized determinant in human antibody/autoantibody responses, and opens the opportunity for more precise personalized use of B cell targeted antibody-based therapy.
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影响因子：
4.4
作者：
Higuchi, T;Aiba, Y;Tsubata, T
通讯作者：
Tsubata, T
DOI：
10.1073/pnas.0703354104
发表时间：
2007-06-05
影响因子：
11.1
作者：
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通讯作者：
Cooper, Max D.
影响因子：
4.4
作者：
Horton, Holly M.;Chu, Seung Y.;Szymkowski, David E.
通讯作者：
Szymkowski, David E.
影响因子：
6.9
作者：
Golde, WT;Gollobin, P;Rodriguez, LL
通讯作者：
Rodriguez, LL
影响因子：
5.6
作者：
Johnson, Syd;Burke, Stephen;Bonvini, Ezio
通讯作者：
Bonvini, Ezio