title: Core fucosylation of μ heavy chains regulates assembly and intracellular signaling of precursor B cell receptors.
abstract: α1,6-Fucosyltransferase (Fut8) knock-out (Fut8(-/-)) mice showed an abnormality in pre-B cell generation. Membrane assembly of pre-BCR is a crucial checkpoint for pre-B cell differentiation and proliferation in both humans and mice. The assembly of pre-BCR on the cell surface was substantially blocked in the Fut8-knockdown pre-B cell line, 70Z/3-KD cells, and then completely restored by re-introduction of the Fut8 gene to 70Z/3-KD (70Z/3-KD-re) cells. Moreover, loss of α1,6-fucosylation (also called core fucosylation) of μHC was associated with the suppression of the interaction between μHC and λ5. In contrast to Fut8(+/+) CD19(+)CD43(-) cells, the subpopulation expressing the μHC·λ5 complex in the Fut8(-/-) CD19(+)CD43(-) cell fraction was decreased. The pre-BCR-mediated tyrosine phosphorylation of CD79a and activation of Btk were attenuated in Fut8-KD cells, and restored in 70Z/3-KD-re cells. The frequency of CD19(low)CD43(-) cells (pre-B cell enriched fraction) was also reduced in Fut8(-/-) bone marrow cells, and then the levels of IgM, IgG, and IgA of 12-week-old Fut8(-/-) mice sera were significantly lower than those of Fut8(+/+) mice. Our results suggest that the core fucosylation of μHC mediates the assembly of pre-BCR to regulate pre-BCR intracellular signaling and pre-B cell proliferation.
authors.affiliation: Institute of Immunology, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Liaoning 116622, China. liwenzhe46@hotmail.com
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Li
authors.forename: Qingping
authors.initials: Q
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Pang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Jin
authors.forename: Huiguo
authors.initials: H
authors.lastname: Wang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Cao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Chi
authors.forename: Renjun
authors.initials: R
authors.lastname: Wang
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kondo
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D005643:Fucose / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase
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