B cell receptor

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The B-cell receptor includes CD79 and an antibody .

The B-cell receptor ( English B-cell receptor , BCR ) is a transmembrane protein and receptor on B cells to which an antibody is bound. The BCR is a central component of the humoral immune response .

properties

After the antibody specifically binds an antigen to the BCR, B cells are activated and, if stimulated by T cell cytokines, are ready for cell division and cell differentiation into B memory cells and B plasma cells . The BCR has two functions, one for signal transduction and one for endocytosis and for initiating the antigen presentation of peptides at MHC-2 . Defects in the BCR lead to an impairment of the production of antibodies and signal transduction, which results in immunodeficiency , autoimmunity or malignancy .

construction

The B-cell receptor consists of a ligand binding function (in consequence also of an oligomerization function ) and a signal transduction function. The ligand is bound by the bound antibody (IgD, IgM, IgA or IgE) and leads to the functions of oligomerization, opsonization , complement activation and neutralization . The signal transduction takes place via the heterodimer CD79 A and B, whose components A and B are connected by disulfide bridges . The signal transduction is increased by a factor of about 100 by binding a coreceptor protein complex made up of CD19 , CD21 (synonym CR2 ) and CD81 (synonym TAPA-1 ). As a result, complement activation can also lead to activation of the BCR. CD79 A and B are transmembrane proteins with ITAM motifs on the cytosolic side for intracellular signal transmission .

Signal transduction

Signal transduction at the BCR.

If the B-cell receptor binds a suitable antigen, the ITAM motifs are phosphorylated by tyrosine kinases of the SRC family, including LYN , FYN and BLK. The tyrosine kinase Syk can bind to the phosphorylated tyrosine residues , which in turn phosphorylates the scaffold protein BLNK at several points. BLNK can now bind further signal proteins that transmit the signal to the cell nucleus. The signal is transmitted via phospholipase C γ (PLC-γ) and NFAT , via the PI3K , via the IKK and NF-κB , and via the ERK . Signal transduction is also influenced by non-coding ribonucleic acids . Via the IKK and NF-κB, the PLC-γ is activated by CD79 and other proteins, then the PLC-γ binds to c-SMAC and hydrolyzes PIP2 to IP3 and diacylglycerol , two secondary messenger substances .

Various mutations of the B-cell receptor are involved in the development of B-cell tumors . This may be due to permanent activation of the BCR, or to differences in oligomerization.

literature

Web links

Individual evidence

  1. ^ Mary Ellen Conley, A. Kerry Dobbs, Dana M. Farmer, Sebnem Kilic, Kenneth Paris, Sofia Grigoriadou, Elaine Coustan-Smith, Vanessa Howard, and Dario Campana: Primary B cell immunodeficiencies: comparisons and contrasts . In: Annual Review of Immunology . 27, 2009. doi : 10.1146 / annurev.immunol.021908.132649 .
  2. ↑ Christopher Goodnow: Multistep pathogenesis of autoimmune disease . In: Cell . 130, No. 1, 2007, pp. 25-35. doi : 10.1016 / j.cell.2007.06.033 . PMID 17632054 .
  3. ^ D Corcos, MJ Osborn, LS Matheson: B-cell receptors and heavy chain diseases: guilty by association? . In: Blood . 117, No. 26, 2011, pp. 6991-6998. doi : 10.1182 / blood-2011-02-336164 . PMID 21508409 .
  4. ^ Kindt, J. Thomas; Goldsby, A. Richard; Osborne, A. Barbara, Janis Kuby: Kuby immunology . WH Freeman, New York 2007, ISBN 1-4292-0211-4 .
  5. ↑ Janeway's immunobiology , 8th. Edition, Garland Science, 2011, ISBN 0815342438 , pp. 258-260.
  6. ↑ a b Tomohiro Kurosaki, Hisaaki Shinohara, Yoshihiro Baba: B Cell Signaling and Fate Decision . In: Annual Review of Immunology . 28, No. 1, 2008, p. 21. doi : 10.1146 / annurev.immunol.021908.132541 .
  7. ↑ a b M. Mraz, TJ Kipps: MicroRNAs and B cell receptor signaling in chronic lymphocytic leukemia. In: Leukemia & Lymphoma . Volume 54, number 8, August 2013, ISSN  1029-2403 , pp. 1836-1839, doi : 10.3109 / 10428194.2013.796055 , PMID 23597135 .
  8. ↑ W. Daneshek, RS Schwartz: Leukemia and auto-immunization- some possible relationships . In: Blood . 14, 1959.
  9. ↑ D. Corcos: Oncogenic potential of the B-cell antigen receptor and its relevance to heavy chain diseases and other B-cell neoplasias: a new model. In: Research in immunology. Volume 141, Number 6, 1990 Jul-Aug, ISSN  0923-2494 , pp. 543-553, PMID 2284498 .
  10. ^ D. Corcos, O. Dunda, C. Butor, JY Cesbron, P. Lorès, D. Bucchini, J. Jami: Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a heavy-chain disease protein . In: Current biology: CB. Volume 5, Number 10, October 1995, ISSN  0960-9822 , pp. 1140-1148, PMID 8548286 .
  11. ↑ RE Davis, VN Ngo, et al .: Chronic active B-cell receptor signaling in diffuse large B-cell lymphoma. In: Nature. Volume 463, number 7277, January 2010, ISSN  1476-4687 , pp. 88-92, doi : 10.1038 / nature08638 . PMID 20054396 , PMC 2845535 (free full text).
  12. ↑ M. Dühren-von Minden, R. Übelhart, D. Schneider, T. Wossning, MP Bach, M. Buchner, D. Hofmann, E. Surova, M. Follo, F. Köhler, H. Wardemann, K. Zirlik , H. Veelken, H. Jumaa: Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signaling. In: Nature. Volume 489, number 7415, September 2012, ISSN  1476-4687 , pp. 309-312, doi : 10.1038 / nature11309 . PMID 22885698 .