Home LiteratureArticle Details
PMID: 8290550 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The alpha/beta sheath and its cytoplasmic tyrosines are required for signaling by the B-cell antigen receptor but not for capping or for serine/threonine-kinase recruitment.

Williams GT, Peaker CJ, Patel KJ, Neuberger MS

Abstract

The B-cell antigen receptor is composed of membrane immunoglobulin sheathed by an alpha/beta heterodimer. The complex is noncovalently associated with protein kinase activity, and crosslinking of the receptor leads to capping and transmembrane signaling. Here we show that the sheath is not necessary either for this capping or for the association of membrane immunoglobulin with the detergent-insoluble cytoskeletal fraction that occurs following crosslinking. It is also not required for association of membrane immunoglobulin with a casein-kinase-like serine/threonine kinase. The sheath is essential, however, for transmembrane signaling. Provision of just the cytoplasmic domain of the beta sheath polypeptide to a mutant, unsheathed IgM molecule was sufficient to restore full signaling capability as judged by the phosphorylation of a variety of cellular proteins, including the B-cell-specific transmembrane protein CD22. This signaling was destroyed by mutating one of the tyrosines in the beta cytoplasmic domain. These results not only suggest that receptor signaling is mediated through phosphorylation of the tyrosines in the sheath's cytoplasmic domains but, together with previous work, indicate that different motifs within the sheath mediate presentation and signaling.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cross-Linking Reagents Cytoplasm/immunology Immunologic Capping Mice Molecular Sequence Data Mutation Phosphorylation Protein Conformation Protein Serine-Threonine Kinases/metabolism Receptors, Antigen, B-Cell/chemistry,genetics,metabolism Signal Transduction/immunology Transfection Tyrosine/chemistry,genetics
Chemicals
Cross-Linking Reagents Receptors, Antigen, B-Cell Tyrosine Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Williams G T
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Peaker C J
Patel K J
Neuberger M S
References (27)
27 references, click to expand
  1. Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2745-9 PMID: 2011584
  2. Antigen presentation by the B cell antigen receptor is driven by the alpha/beta sheath and occurs independently of its cytoplasmic tyrosines.
    Cell. 1993 Sep 10;74(5):939-46 PMID: 8374958
  3. The mouse B-cell antigen receptor: definition and assembly of the core receptor of the five immunoglobulin isotypes.
    Immunol Rev. 1993 Apr;132:147-61 PMID: 8349294
  4. Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles.
    J Immunol. 1993 Jul 1;151(1):175-87 PMID: 8100843
  5. Membrane immunoglobulin without sheath or anchor.
    Mol Immunol. 1993 Nov;30(16):1427-32 PMID: 8232328
  6. Membrane and cytoplasmic changes in B lymphocytes induced by ligand-surface immunoglobulin interaction.
    Adv Immunol. 1976;24:37-165 PMID: 798475
  7. Ligand-induced association of surface immunoglobulin with the detergent-insoluble cytoskeletal matrix of the B lymphocyte.
    J Immunol. 1982 Mar;128(3):1198-204 PMID: 6976988
  8. Lyb-8.2: A new B cell antigen defined and characterized with a monoclonal antibody.
    Immunogenetics. 1982;16(5):381-91 PMID: 6984010
  9. B lymphocyte receptors and polyphosphoinositide degradation.
    Cell. 1985 Jul;41(3):999-1006 PMID: 2408764
  10. CD19 is functionally and physically associated with surface immunoglobulin.
    J Exp Med. 1989 Dec 1;170(6):2159-64 PMID: 2479707
  11. The sequence of the mu transmembrane segment determines the tissue specificity of the transport of immunoglobulin M to the cell surface.
    J Exp Med. 1990 Mar 1;171(3):947-52 PMID: 2106568
  12. The role of class II molecules in human B cell activation. Association with phosphatidyl inositol turnover, protein tyrosine phosphorylation, and proliferation.
    J Immunol. 1990 May 15;144(10):3684-92 PMID: 1692059
  13. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin.
    EMBO J. 1990 Jul;9(7):2125-31 PMID: 2357961
  14. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor.
    Nature. 1990 Jun 28;345(6278):810-3 PMID: 1694265
  15. Identification of two distinct phosphoproteins as components of the human B cell antigen receptor complex.
    Eur J Immunol. 1990 Dec;20(12):2789-93 PMID: 2269333
  16. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  17. The B-cell antigen receptor of the five immunoglobulin classes.
    Nature. 1991 Aug 29;352(6338):777-81 PMID: 1881434
  18. Glycosyl-phosphatidylinositol linkage as a mechanism for cell-surface expression of immunoglobulin D.
    Nature. 1992 Mar 19;356(6366):246-8 PMID: 1313152
  19. Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1.
    Mol Biol Cell. 1992 Mar;3(3):275-86 PMID: 1627830
  20. Examination of B lymphoid cell lines for membrane immunoglobulin-stimulated tyrosine phosphorylation and src-family tyrosine kinase mRNA expression.
    Mol Immunol. 1992 Jul-Aug;29(7-8):917-26 PMID: 1378935
  21. Characterization of molecular components associated with surface immunoglobulin M in human B lymphocytes: presence of tyrosine and serine/threonine protein kinases.
    Eur J Immunol. 1992 Aug;22(8):2093-9 PMID: 1386314
  22. The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors.
    Science. 1992 Oct 2;258(5079):123-6 PMID: 1439759
  23. Tyrosine phosphorylation of CD22 during B cell activation.
    Science. 1992 Nov 6;258(5084):1001-4 PMID: 1279802
  24. In situ analyses of in ovo graft-vs.-host reaction induced by thymic nurse cell lymphocytes.
    Eur J Immunol. 1993 Apr;23(4):904-10 PMID: 8096184
  25. CD22 associates with the human surface IgM-B-cell antigen receptor complex.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3236-40 PMID: 8475064
  26. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases.
    Cell. 1993 Apr 23;73(2):209-12 PMID: 8477442
  27. Tyrosine phosphorylation of components of the B-cell antigen receptors following receptor crosslinking.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3436-40 PMID: 1707541
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-01-18
Pages
474-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42971
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]