Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

BLNK Deficiency

  • Vassilios Lougaris
  • Alessandro PlebaniEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_18-1


B-cell linker protein (BLNK) deficiency (OMIM #613502) is a rare primary immunodeficiency characterized by reduced serum levels of all immunoglobulin classes in the absence of peripheral B cells (peripheral B cells <2%). To date, a small number of patients have been described. BLNK deficiency is caused by biallelic deleterious mutations in the gene encoding for BLNK.


Early B cell development takes place in the bone marrow. An important maturational step is the progression form the pro-B to the pre-B stage (Espeli et al. 2006; Rudin and Thompson 1998; Bartholdy and Matthias 2004). This passage depends on the expression of a functional B cell receptor composed of the μ heavy chain (IGHM; OMIM*147020), Igα (CD79A; OMIM*112205), Igβ (CD79B; OMIM*147245), VpreB, and λ5 (IGLL1; OMIM*146770) that initiates downstream signalling necessary for early B cell differentiation through kinases such as BTK and BLNK (OMIM*604615). Over the years, animal models and in vitro...

This is a preview of subscription content, log in to check access.


  1. Bartholdy B, Matthias P. Transcriptional control of B cell development and function. Gene. 2004;327:1–23.CrossRefGoogle Scholar
  2. Conley ME, Cooper MD. Genetic basis of abnormal B cell development. Curr Opin Immunol. 1998;10(4):339–406.CrossRefGoogle Scholar
  3. Espeli M, Rossi B, Mancini SJ, Roche P, Gauthier L, Schiff C. Initiation of pre-B cell receptor signaling: common and distinctive features in human and mouse. Semin Immunol. 2006;18:56–66.CrossRefGoogle Scholar
  4. Lagresle-Peyrou C, Millili M, Luce S, Boned A, Sadek H, Rouiller J, Frange P, Cros G, Cavazzana M, André-Schmutz I, Schiff C. The BLNK adaptor protein has a nonredundant role in human B-cell difefrentiation. J Allergy Clin Immunol. 2014;134(1): 145–54.CrossRefGoogle Scholar
  5. Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D, Chan AC, Conley ME. An essential role for BLNK in human B cell development. Science. 1999;286:1954–7.CrossRefGoogle Scholar
  6. Naser Eddin A, Shamriz O, Keller B, Alzyoud RM, Unger S, Fisch P, Prus E, Berkun Y, Averbuch D, Shaag A, Wahadneh AM, Conley ME, Warnatz K, Elpeleg O, Stepensky P. Enteroviral infection in a patient with BLNK adaptor protein deficiency. J Clin Immunol. 2015;35(4):356–60.CrossRefGoogle Scholar
  7. Rudin CM, Thompson CB. B-cell development and maturation. Semin Oncol. 1998;25:435–46.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental SciencesUniversity of Brescia and ASST-Spedali Civili of BresciaBresciaItaly

Section editors and affiliations

  • Klaus Warnatz
    • 1
  • Joris M. van Montfrans
    • 2
  1. 1.Center for Chronic ImmunodeficiencyUniversity Medical Center and University of FreiburgFreiburgGermany
  2. 2.UMC UtrechtUtrechtNetherlands