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...