FcμR interacts and cooperates with the B cell receptor To promote B cell survival.
The IgM FcR (FcμR) promotes B cell survival, but the molecular mechanism remains largely unknown. We show using FcμR(-/-) and wild-type mice that FcμR specifically enhanced B cell survival induced by BCR cross-linking with F(ab')2-anti-IgM Abs while having no effect on survival when the B cells were activated by CD40 ligation or LPS stimulation. FcμR expression was markedly upregulated by anti-IgM stimulation, which may promote enhanced FcμR signaling in these cells. Immunofluorescence and confocal microscopy analyses demonstrated that FcμR colocalized with the BCR on the plasma membrane of primary B cells. Coimmunoprecipitation analysis further revealed that FcμR physically interacted with the BCR complex. Because NF-κB plays a prominent role in B cell survival, we analyzed whether FcμR was involved in BCR-triggered NF-κB activation. FcμR did not affect BCR-triggered IκBα phosphorylation characteristic of the canonical NF-κB activation pathway but promoted the production of the noncanonical NF-κB pathway component p52. Consistent with the elevated p52 levels, FcμR enhanced BCR-triggered expression of the antiapoptotic protein BCL-xL. Importantly, FcμR stimulation alone in the absence of BCR signaling had no effect on either IκBα phosphorylation or the expression of p52 and BCL-xL. Therefore, FcμR relied on the BCR signal to activate the noncanonical NF-κB pathway and enhance B cell survival. These results reveal a cross-talk downstream of FcμR and BCR signaling and provide mechanistic insight into FcμR-mediated enhancement of B cell survival after BCR stimulation.
Laboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama 230-0045, Japan;
Rika
R
Ouchida
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
Qing
Q
Lu
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
Jun
J
Liu
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
Yingqian
Y
Li
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
Yiwei
Y
Chu
Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;
Takeshi
T
Tsubata
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Biotherapy Research Center, Fudan University, Shanghai 200032, China; and Immunobiology Institute, Fudan University, Shanghai 200032, China wang@fudan.edu.cn.
Ji-Yang
JY
Wang
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D052003:NF-kappa B p52 Subunit; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C044203:anti-IgM; D051020:bcl-X Protein